TW202307212A - 對抗廣譜冠狀病毒變種的信使rna疫苗 - Google Patents
對抗廣譜冠狀病毒變種的信使rna疫苗 Download PDFInfo
- Publication number
- TW202307212A TW202307212A TW111113932A TW111113932A TW202307212A TW 202307212 A TW202307212 A TW 202307212A TW 111113932 A TW111113932 A TW 111113932A TW 111113932 A TW111113932 A TW 111113932A TW 202307212 A TW202307212 A TW 202307212A
- Authority
- TW
- Taiwan
- Prior art keywords
- leu
- ser
- val
- thr
- asn
- Prior art date
Links
- 108700021021 mRNA Vaccine Proteins 0.000 title claims abstract description 64
- 241000711573 Coronaviridae Species 0.000 title claims abstract description 41
- 238000001228 spectrum Methods 0.000 title description 3
- 229960005486 vaccine Drugs 0.000 claims abstract description 90
- 229940126582 mRNA vaccine Drugs 0.000 claims abstract description 61
- 108020003175 receptors Proteins 0.000 claims abstract description 17
- 102000005962 receptors Human genes 0.000 claims abstract description 17
- 238000012217 deletion Methods 0.000 claims abstract description 6
- 230000037430 deletion Effects 0.000 claims abstract description 5
- 108020004999 messenger RNA Proteins 0.000 claims description 163
- 239000002105 nanoparticle Substances 0.000 claims description 85
- 101710198474 Spike protein Proteins 0.000 claims description 65
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 58
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 56
- 108020004707 nucleic acids Proteins 0.000 claims description 56
- 102000039446 nucleic acids Human genes 0.000 claims description 56
- 150000007523 nucleic acids Chemical class 0.000 claims description 56
- 229940096437 Protein S Drugs 0.000 claims description 53
- 239000002773 nucleotide Substances 0.000 claims description 49
- 125000003729 nucleotide group Chemical group 0.000 claims description 49
- 230000013595 glycosylation Effects 0.000 claims description 43
- 238000006206 glycosylation reaction Methods 0.000 claims description 43
- 108020004414 DNA Proteins 0.000 claims description 41
- 150000002632 lipids Chemical class 0.000 claims description 40
- 229920000642 polymer Polymers 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 27
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 24
- 229920001577 copolymer Polymers 0.000 claims description 24
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 24
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 23
- 230000002163 immunogen Effects 0.000 claims description 23
- 235000001014 amino acid Nutrition 0.000 claims description 22
- 238000006467 substitution reaction Methods 0.000 claims description 22
- 230000005867 T cell response Effects 0.000 claims description 21
- 101000629318 Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein Proteins 0.000 claims description 19
- 230000003053 immunization Effects 0.000 claims description 16
- 238000002649 immunization Methods 0.000 claims description 15
- 150000004676 glycans Chemical class 0.000 claims description 14
- 239000002502 liposome Substances 0.000 claims description 11
- 208000001528 Coronaviridae Infections Diseases 0.000 claims description 9
- 230000004988 N-glycosylation Effects 0.000 claims description 9
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 claims description 8
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 claims description 8
- 101150112743 HSPA5 gene Proteins 0.000 claims description 8
- 101000666295 Homo sapiens X-box-binding protein 1 Proteins 0.000 claims description 8
- 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 claims description 8
- 102100038151 X-box-binding protein 1 Human genes 0.000 claims description 8
- 229940024606 amino acid Drugs 0.000 claims description 8
- 101150028578 grp78 gene Proteins 0.000 claims description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
- 102000053602 DNA Human genes 0.000 claims description 7
- 230000004989 O-glycosylation Effects 0.000 claims description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 6
- 206010022000 influenza Diseases 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- 229940022962 COVID-19 vaccine Drugs 0.000 claims description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 238000007792 addition Methods 0.000 claims description 4
- 229940001442 combination vaccine Drugs 0.000 claims description 4
- 235000009566 rice Nutrition 0.000 claims description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 3
- 241000193738 Bacillus anthracis Species 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
- 229940124859 Rotavirus vaccine Drugs 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- 229940124858 Streptococcus pneumoniae vaccine Drugs 0.000 claims description 3
- 229940021704 adenovirus vaccine Drugs 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- 230000006907 apoptotic process Effects 0.000 claims description 3
- 235000009582 asparagine Nutrition 0.000 claims description 3
- 229960001230 asparagine Drugs 0.000 claims description 3
- 229960005004 cholera vaccine Drugs 0.000 claims description 3
- 229960005097 diphtheria vaccines Drugs 0.000 claims description 3
- 229960004443 hemophilus influenzae b vaccines Drugs 0.000 claims description 3
- 208000005252 hepatitis A Diseases 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 claims description 3
- 229940041323 measles vaccine Drugs 0.000 claims description 3
- 229940095293 mumps vaccine Drugs 0.000 claims description 3
- 239000007922 nasal spray Substances 0.000 claims description 3
- 229940097496 nasal spray Drugs 0.000 claims description 3
- 229960002566 papillomavirus vaccine Drugs 0.000 claims description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 3
- 229940083538 smallpox vaccine Drugs 0.000 claims description 3
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims description 3
- 229960002109 tuberculosis vaccine Drugs 0.000 claims description 3
- 230000003827 upregulation Effects 0.000 claims description 3
- 230000033289 adaptive immune response Effects 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 235000013922 glutamic acid Nutrition 0.000 claims description 2
- 239000004220 glutamic acid Substances 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 241000209094 Oryza Species 0.000 claims 3
- 239000002777 nucleoside Substances 0.000 claims 2
- 125000003835 nucleoside group Chemical group 0.000 claims 2
- 230000001568 sexual effect Effects 0.000 claims 2
- 241000004176 Alphacoronavirus Species 0.000 claims 1
- 241000008904 Betacoronavirus Species 0.000 claims 1
- 241000008920 Gammacoronavirus Species 0.000 claims 1
- 230000028993 immune response Effects 0.000 abstract description 25
- 230000001681 protective effect Effects 0.000 abstract description 13
- 108010061994 Coronavirus Spike Glycoprotein Proteins 0.000 abstract description 12
- 102100031673 Corneodesmosin Human genes 0.000 description 78
- 101710139375 Corneodesmosin Proteins 0.000 description 78
- 108090000623 proteins and genes Proteins 0.000 description 64
- 210000004027 cell Anatomy 0.000 description 63
- 102000004169 proteins and genes Human genes 0.000 description 63
- 235000018102 proteins Nutrition 0.000 description 57
- 235000000346 sugar Nutrition 0.000 description 57
- 241001678559 COVID-19 virus Species 0.000 description 49
- 108091028043 Nucleic acid sequence Proteins 0.000 description 42
- 108010061238 threonyl-glycine Proteins 0.000 description 39
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 36
- 108010050848 glycylleucine Proteins 0.000 description 33
- 241000700605 Viruses Species 0.000 description 30
- 108010037850 glycylvaline Proteins 0.000 description 27
- 230000035772 mutation Effects 0.000 description 27
- 210000001744 T-lymphocyte Anatomy 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 25
- RAQMSGVCGSJKCL-FOHZUACHSA-N Asn-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(N)=O RAQMSGVCGSJKCL-FOHZUACHSA-N 0.000 description 24
- TZCGZYWNIDZZMR-UHFFFAOYSA-N Ile-Arg-Ala Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(C)C(O)=O)CCCN=C(N)N TZCGZYWNIDZZMR-UHFFFAOYSA-N 0.000 description 24
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 24
- 241000880493 Leptailurus serval Species 0.000 description 24
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 24
- GHKXHCMRAUYLBS-CIUDSAMLSA-N Lys-Ser-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O GHKXHCMRAUYLBS-CIUDSAMLSA-N 0.000 description 24
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 24
- 108010079364 N-glycylalanine Proteins 0.000 description 24
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 24
- 108010057821 leucylproline Proteins 0.000 description 24
- 108010073969 valyllysine Proteins 0.000 description 24
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 21
- HHOOEUSPFGPZFP-QWRGUYRKSA-N Phe-Asn-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O HHOOEUSPFGPZFP-QWRGUYRKSA-N 0.000 description 21
- 210000004443 dendritic cell Anatomy 0.000 description 20
- 238000001890 transfection Methods 0.000 description 20
- ZYVTXBXHIKGZMD-QSFUFRPTSA-N Ile-Val-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ZYVTXBXHIKGZMD-QSFUFRPTSA-N 0.000 description 19
- 208000015181 infectious disease Diseases 0.000 description 19
- ZVFVBBGVOILKPO-WHFBIAKZSA-N Ala-Gly-Ala Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O ZVFVBBGVOILKPO-WHFBIAKZSA-N 0.000 description 18
- IVPNEDNYYYFAGI-GARJFASQSA-N Asp-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N IVPNEDNYYYFAGI-GARJFASQSA-N 0.000 description 18
- UMYZBHKAVTXWIW-GMOBBJLQSA-N Ile-Asp-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UMYZBHKAVTXWIW-GMOBBJLQSA-N 0.000 description 18
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 18
- 108010044940 alanylglutamine Proteins 0.000 description 18
- 108010038633 aspartylglutamate Proteins 0.000 description 18
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 18
- 108010017391 lysylvaline Proteins 0.000 description 18
- 108010051242 phenylalanylserine Proteins 0.000 description 18
- QICVAHODWHIWIS-HTFCKZLJSA-N Ile-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N QICVAHODWHIWIS-HTFCKZLJSA-N 0.000 description 17
- 210000002706 plastid Anatomy 0.000 description 17
- KXFCBAHYSLJCCY-ZLUOBGJFSA-N Asn-Asn-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O KXFCBAHYSLJCCY-ZLUOBGJFSA-N 0.000 description 16
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 16
- RMKGXGPQIPLTFC-KKUMJFAQSA-N Phe-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O RMKGXGPQIPLTFC-KKUMJFAQSA-N 0.000 description 16
- 230000003248 secreting effect Effects 0.000 description 16
- 238000001262 western blot Methods 0.000 description 16
- IARGXWMWRFOQPG-GCJQMDKQSA-N Asn-Ala-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IARGXWMWRFOQPG-GCJQMDKQSA-N 0.000 description 15
- WQAOZCVOOYUWKG-LSJOCFKGSA-N Asn-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC(=O)N)N WQAOZCVOOYUWKG-LSJOCFKGSA-N 0.000 description 15
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 15
- DBSLVQBXKVKDKJ-BJDJZHNGSA-N Leu-Ile-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DBSLVQBXKVKDKJ-BJDJZHNGSA-N 0.000 description 15
- OSBADCBXAMSPQD-YESZJQIVSA-N Phe-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N OSBADCBXAMSPQD-YESZJQIVSA-N 0.000 description 15
- OJRNZRROAIAHDL-LKXGYXEUSA-N Thr-Asn-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OJRNZRROAIAHDL-LKXGYXEUSA-N 0.000 description 15
- 108010087823 glycyltyrosine Proteins 0.000 description 15
- 230000003472 neutralizing effect Effects 0.000 description 15
- 108010029020 prolylglycine Proteins 0.000 description 15
- 108010009962 valyltyrosine Proteins 0.000 description 15
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 14
- 108010005233 alanylglutamic acid Proteins 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 14
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 13
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- GJLXVWOMRRWCIB-MERZOTPQSA-N (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=C(O)C=C1 GJLXVWOMRRWCIB-MERZOTPQSA-N 0.000 description 12
- DQVAZKGVGKHQDS-UHFFFAOYSA-N 2-[[1-[2-[(2-amino-4-methylpentanoyl)amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoic acid Chemical compound CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(CC(C)C)C(O)=O DQVAZKGVGKHQDS-UHFFFAOYSA-N 0.000 description 12
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 12
- UGLPMYSCWHTZQU-AUTRQRHGSA-N Ala-Ala-Tyr Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 UGLPMYSCWHTZQU-AUTRQRHGSA-N 0.000 description 12
- SUMYEVXWCAYLLJ-GUBZILKMSA-N Ala-Leu-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O SUMYEVXWCAYLLJ-GUBZILKMSA-N 0.000 description 12
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 12
- ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 description 12
- BECXEHHOZNFFFX-IHRRRGAJSA-N Arg-Ser-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BECXEHHOZNFFFX-IHRRRGAJSA-N 0.000 description 12
- APHUDFFMXFYRKP-CIUDSAMLSA-N Asn-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)N)N APHUDFFMXFYRKP-CIUDSAMLSA-N 0.000 description 12
- XSGBIBGAMKTHMY-WHFBIAKZSA-N Asn-Asp-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O XSGBIBGAMKTHMY-WHFBIAKZSA-N 0.000 description 12
- QNJIRRVTOXNGMH-GUBZILKMSA-N Asn-Gln-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(N)=O QNJIRRVTOXNGMH-GUBZILKMSA-N 0.000 description 12
- QPTAGIPWARILES-AVGNSLFASA-N Asn-Gln-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QPTAGIPWARILES-AVGNSLFASA-N 0.000 description 12
- IBLAOXSULLECQZ-IUKAMOBKSA-N Asn-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(N)=O IBLAOXSULLECQZ-IUKAMOBKSA-N 0.000 description 12
- NCFJQJRLQJEECD-NHCYSSNCSA-N Asn-Leu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O NCFJQJRLQJEECD-NHCYSSNCSA-N 0.000 description 12
- VHQSGALUSWIYOD-QXEWZRGKSA-N Asn-Pro-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O VHQSGALUSWIYOD-QXEWZRGKSA-N 0.000 description 12
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 12
- KLYPOCBLKMPBIQ-GHCJXIJMSA-N Asp-Ile-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N KLYPOCBLKMPBIQ-GHCJXIJMSA-N 0.000 description 12
- XUVTWGPERWIERB-IHRRRGAJSA-N Asp-Pro-Phe Chemical compound N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O XUVTWGPERWIERB-IHRRRGAJSA-N 0.000 description 12
- JLZCAZJGWNRXCI-XKBZYTNZSA-N Cys-Thr-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O JLZCAZJGWNRXCI-XKBZYTNZSA-N 0.000 description 12
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 12
- ZDJZEGYVKANKED-NRPADANISA-N Gln-Cys-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O ZDJZEGYVKANKED-NRPADANISA-N 0.000 description 12
- ZBKUIQNCRIYVGH-SDDRHHMPSA-N Gln-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZBKUIQNCRIYVGH-SDDRHHMPSA-N 0.000 description 12
- LPIKVBWNNVFHCQ-GUBZILKMSA-N Gln-Ser-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LPIKVBWNNVFHCQ-GUBZILKMSA-N 0.000 description 12
- NHMRJKKAVMENKJ-WDCWCFNPSA-N Gln-Thr-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NHMRJKKAVMENKJ-WDCWCFNPSA-N 0.000 description 12
- XKPACHRGOWQHFH-IRIUXVKKSA-N Gln-Thr-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XKPACHRGOWQHFH-IRIUXVKKSA-N 0.000 description 12
- SGVGIVDZLSHSEN-RYUDHWBXSA-N Gln-Tyr-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O SGVGIVDZLSHSEN-RYUDHWBXSA-N 0.000 description 12
- FQFWFZWOHOEVMZ-IHRRRGAJSA-N Glu-Phe-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O FQFWFZWOHOEVMZ-IHRRRGAJSA-N 0.000 description 12
- FVGOGEGGQLNZGH-DZKIICNBSA-N Glu-Val-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FVGOGEGGQLNZGH-DZKIICNBSA-N 0.000 description 12
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 12
- XBWMTPAIUQIWKA-BYULHYEWSA-N Gly-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN XBWMTPAIUQIWKA-BYULHYEWSA-N 0.000 description 12
- LCNXZQROPKFGQK-WHFBIAKZSA-N Gly-Asp-Ser Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O LCNXZQROPKFGQK-WHFBIAKZSA-N 0.000 description 12
- LHYJCVCQPWRMKZ-WEDXCCLWSA-N Gly-Leu-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LHYJCVCQPWRMKZ-WEDXCCLWSA-N 0.000 description 12
- WTUSRDZLLWGYAT-KCTSRDHCSA-N Gly-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN WTUSRDZLLWGYAT-KCTSRDHCSA-N 0.000 description 12
- ILUVWFTXAUYOBW-CUJWVEQBSA-N His-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)N)O ILUVWFTXAUYOBW-CUJWVEQBSA-N 0.000 description 12
- TZCGZYWNIDZZMR-NAKRPEOUSA-N Ile-Arg-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](C)C(=O)O)N TZCGZYWNIDZZMR-NAKRPEOUSA-N 0.000 description 12
- APDIECQNNDGFPD-PYJNHQTQSA-N Ile-His-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N APDIECQNNDGFPD-PYJNHQTQSA-N 0.000 description 12
- KYLIZSDYWQQTFM-PEDHHIEDSA-N Ile-Ile-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CCCN=C(N)N KYLIZSDYWQQTFM-PEDHHIEDSA-N 0.000 description 12
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 12
- WNGVUZWBXZKQES-YUMQZZPRSA-N Leu-Ala-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O WNGVUZWBXZKQES-YUMQZZPRSA-N 0.000 description 12
- VCSBGUACOYUIGD-CIUDSAMLSA-N Leu-Asn-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VCSBGUACOYUIGD-CIUDSAMLSA-N 0.000 description 12
- APFJUBGRZGMQFF-QWRGUYRKSA-N Leu-Gly-Lys Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCCN APFJUBGRZGMQFF-QWRGUYRKSA-N 0.000 description 12
- LIINDKYIGYTDLG-PPCPHDFISA-N Leu-Ile-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LIINDKYIGYTDLG-PPCPHDFISA-N 0.000 description 12
- RTIRBWJPYJYTLO-MELADBBJSA-N Leu-Lys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N RTIRBWJPYJYTLO-MELADBBJSA-N 0.000 description 12
- GCXGCIYIHXSKAY-ULQDDVLXSA-N Leu-Phe-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GCXGCIYIHXSKAY-ULQDDVLXSA-N 0.000 description 12
- XXXXOVFBXRERQL-ULQDDVLXSA-N Leu-Pro-Phe Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XXXXOVFBXRERQL-ULQDDVLXSA-N 0.000 description 12
- BRTVHXHCUSXYRI-CIUDSAMLSA-N Leu-Ser-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O BRTVHXHCUSXYRI-CIUDSAMLSA-N 0.000 description 12
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 12
- VHTIZYYHIUHMCA-JYJNAYRXSA-N Leu-Tyr-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VHTIZYYHIUHMCA-JYJNAYRXSA-N 0.000 description 12
- VJGQRELPQWNURN-JYJNAYRXSA-N Leu-Tyr-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O VJGQRELPQWNURN-JYJNAYRXSA-N 0.000 description 12
- FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 0.000 description 12
- WALVCOOOKULCQM-ULQDDVLXSA-N Lys-Arg-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WALVCOOOKULCQM-ULQDDVLXSA-N 0.000 description 12
- UWHCKWNPWKTMBM-WDCWCFNPSA-N Lys-Thr-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O UWHCKWNPWKTMBM-WDCWCFNPSA-N 0.000 description 12
- QFSYGUMEANRNJE-DCAQKATOSA-N Lys-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N QFSYGUMEANRNJE-DCAQKATOSA-N 0.000 description 12
- HUURTRNKPBHHKZ-JYJNAYRXSA-N Met-Phe-Val Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 HUURTRNKPBHHKZ-JYJNAYRXSA-N 0.000 description 12
- OMHMIXFFRPMYHB-SRVKXCTJSA-N Phe-Cys-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OMHMIXFFRPMYHB-SRVKXCTJSA-N 0.000 description 12
- QPVFUAUFEBPIPT-CDMKHQONSA-N Phe-Gly-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O QPVFUAUFEBPIPT-CDMKHQONSA-N 0.000 description 12
- PMKIMKUGCSVFSV-CQDKDKBSSA-N Phe-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=CC=C2)N PMKIMKUGCSVFSV-CQDKDKBSSA-N 0.000 description 12
- INHMISZWLJZQGH-ULQDDVLXSA-N Phe-Leu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 INHMISZWLJZQGH-ULQDDVLXSA-N 0.000 description 12
- GPLWGAYGROGDEN-BZSNNMDCSA-N Phe-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GPLWGAYGROGDEN-BZSNNMDCSA-N 0.000 description 12
- LCRSGSIRKLXZMZ-BPNCWPANSA-N Pro-Ala-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LCRSGSIRKLXZMZ-BPNCWPANSA-N 0.000 description 12
- XKHCJJPNXFBADI-DCAQKATOSA-N Pro-Asp-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O XKHCJJPNXFBADI-DCAQKATOSA-N 0.000 description 12
- 241001112090 Pseudovirus Species 0.000 description 12
- MWMKFWJYRRGXOR-ZLUOBGJFSA-N Ser-Ala-Asn Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC(N)=O)C)CO MWMKFWJYRRGXOR-ZLUOBGJFSA-N 0.000 description 12
- HRNQLKCLPVKZNE-CIUDSAMLSA-N Ser-Ala-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O HRNQLKCLPVKZNE-CIUDSAMLSA-N 0.000 description 12
- SNNSYBWPPVAXQW-ZLUOBGJFSA-N Ser-Cys-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)O)N)O SNNSYBWPPVAXQW-ZLUOBGJFSA-N 0.000 description 12
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 12
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 12
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 12
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 12
- TWLMXDWFVNEFFK-FJXKBIBVSA-N Thr-Arg-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O TWLMXDWFVNEFFK-FJXKBIBVSA-N 0.000 description 12
- WFUAUEQXPVNAEF-ZJDVBMNYSA-N Thr-Arg-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CCCN=C(N)N WFUAUEQXPVNAEF-ZJDVBMNYSA-N 0.000 description 12
- JMGJDTNUMAZNLX-RWRJDSDZSA-N Thr-Glu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JMGJDTNUMAZNLX-RWRJDSDZSA-N 0.000 description 12
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 12
- RRRRCRYTLZVCEN-HJGDQZAQSA-N Thr-Leu-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O RRRRCRYTLZVCEN-HJGDQZAQSA-N 0.000 description 12
- WVGKPKDWYQXWLU-BZSNNMDCSA-N Tyr-His-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCCN)C(=O)O)N)O WVGKPKDWYQXWLU-BZSNNMDCSA-N 0.000 description 12
- NKUGCYDFQKFVOJ-JYJNAYRXSA-N Tyr-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NKUGCYDFQKFVOJ-JYJNAYRXSA-N 0.000 description 12
- NWEGIYMHTZXVBP-JSGCOSHPSA-N Tyr-Val-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O NWEGIYMHTZXVBP-JSGCOSHPSA-N 0.000 description 12
- WBAJDGWKRIHOAC-GVXVVHGQSA-N Val-Lys-Gln Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O WBAJDGWKRIHOAC-GVXVVHGQSA-N 0.000 description 12
- VNGKMNPAENRGDC-JYJNAYRXSA-N Val-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=CC=C1 VNGKMNPAENRGDC-JYJNAYRXSA-N 0.000 description 12
- QSPOLEBZTMESFY-SRVKXCTJSA-N Val-Pro-Val Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O QSPOLEBZTMESFY-SRVKXCTJSA-N 0.000 description 12
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 12
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 12
- PGBMPFKFKXYROZ-UFYCRDLUSA-N Val-Tyr-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N PGBMPFKFKXYROZ-UFYCRDLUSA-N 0.000 description 12
- IECQJCJNPJVUSB-IHRRRGAJSA-N Val-Tyr-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(O)=O IECQJCJNPJVUSB-IHRRRGAJSA-N 0.000 description 12
- OWFGFHQMSBTKLX-UFYCRDLUSA-N Val-Tyr-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N OWFGFHQMSBTKLX-UFYCRDLUSA-N 0.000 description 12
- DFQZDQPLWBSFEJ-LSJOCFKGSA-N Val-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)O)N DFQZDQPLWBSFEJ-LSJOCFKGSA-N 0.000 description 12
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 12
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 12
- 108010041407 alanylaspartic acid Proteins 0.000 description 12
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 12
- 108010054812 diprotin A Proteins 0.000 description 12
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 12
- 108010073628 glutamyl-valyl-phenylalanine Proteins 0.000 description 12
- 108010090037 glycyl-alanyl-isoleucine Proteins 0.000 description 12
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 12
- 108010027338 isoleucylcysteine Proteins 0.000 description 12
- 108010090333 leucyl-lysyl-proline Proteins 0.000 description 12
- 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 description 12
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 12
- 108010009298 lysylglutamic acid Proteins 0.000 description 12
- 238000006386 neutralization reaction Methods 0.000 description 12
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 12
- 108010064486 phenylalanyl-leucyl-valine Proteins 0.000 description 12
- 108010089198 phenylalanyl-prolyl-arginine Proteins 0.000 description 12
- 108010012581 phenylalanylglutamate Proteins 0.000 description 12
- 108010020432 prolyl-prolylisoleucine Proteins 0.000 description 12
- SGYSTDWPNPKJPP-GUBZILKMSA-N Arg-Ala-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SGYSTDWPNPKJPP-GUBZILKMSA-N 0.000 description 11
- 102000001398 Granzyme Human genes 0.000 description 11
- 108060005986 Granzyme Proteins 0.000 description 11
- FRPNVPKQVFHSQY-BPUTZDHNSA-N Ser-Trp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CO)N FRPNVPKQVFHSQY-BPUTZDHNSA-N 0.000 description 11
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 108010056582 methionylglutamic acid Proteins 0.000 description 11
- 230000004906 unfolded protein response Effects 0.000 description 11
- TWPCWKVOZDUYAA-KKUMJFAQSA-N Lys-Phe-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O TWPCWKVOZDUYAA-KKUMJFAQSA-N 0.000 description 10
- WVXQQUWOKUZIEG-VEVYYDQMSA-N Pro-Thr-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O WVXQQUWOKUZIEG-VEVYYDQMSA-N 0.000 description 10
- 108010047495 alanylglycine Proteins 0.000 description 10
- 238000013461 design Methods 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 210000004988 splenocyte Anatomy 0.000 description 10
- CWFMWBHMIMNZLN-NAKRPEOUSA-N (2s)-1-[(2s)-2-[[(2s,3s)-2-amino-3-methylpentanoyl]amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CWFMWBHMIMNZLN-NAKRPEOUSA-N 0.000 description 9
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 9
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 9
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 9
- BUDNAJYVCUHLSV-ZLUOBGJFSA-N Ala-Asp-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O BUDNAJYVCUHLSV-ZLUOBGJFSA-N 0.000 description 9
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 9
- AWAXZRDKUHOPBO-GUBZILKMSA-N Ala-Gln-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O AWAXZRDKUHOPBO-GUBZILKMSA-N 0.000 description 9
- ZDYNWWQXFRUOEO-XDTLVQLUSA-N Ala-Gln-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDYNWWQXFRUOEO-XDTLVQLUSA-N 0.000 description 9
- NJPMYXWVWQWCSR-ACZMJKKPSA-N Ala-Glu-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NJPMYXWVWQWCSR-ACZMJKKPSA-N 0.000 description 9
- BVSGPHDECMJBDE-HGNGGELXSA-N Ala-Glu-His Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N BVSGPHDECMJBDE-HGNGGELXSA-N 0.000 description 9
- LJFNNUBZSZCZFN-WHFBIAKZSA-N Ala-Gly-Cys Chemical compound N[C@@H](C)C(=O)NCC(=O)N[C@@H](CS)C(=O)O LJFNNUBZSZCZFN-WHFBIAKZSA-N 0.000 description 9
- FAJIYNONGXEXAI-CQDKDKBSSA-N Ala-His-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 FAJIYNONGXEXAI-CQDKDKBSSA-N 0.000 description 9
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 9
- IPZQNYYAYVRKKK-FXQIFTODSA-N Ala-Pro-Ala Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IPZQNYYAYVRKKK-FXQIFTODSA-N 0.000 description 9
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 9
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 9
- IETUUAHKCHOQHP-KZVJFYERSA-N Ala-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)C(O)=O IETUUAHKCHOQHP-KZVJFYERSA-N 0.000 description 9
- MTDDMSUUXNQMKK-BPNCWPANSA-N Ala-Tyr-Arg Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N MTDDMSUUXNQMKK-BPNCWPANSA-N 0.000 description 9
- QRIYOHQJRDHFKF-UWJYBYFXSA-N Ala-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 QRIYOHQJRDHFKF-UWJYBYFXSA-N 0.000 description 9
- JSHVMZANPXCDTL-GMOBBJLQSA-N Arg-Asp-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JSHVMZANPXCDTL-GMOBBJLQSA-N 0.000 description 9
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 9
- CZUHPNLXLWMYMG-UBHSHLNASA-N Arg-Phe-Ala Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 CZUHPNLXLWMYMG-UBHSHLNASA-N 0.000 description 9
- VEAIMHJZTIDCIH-KKUMJFAQSA-N Arg-Phe-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEAIMHJZTIDCIH-KKUMJFAQSA-N 0.000 description 9
- LXMKTIZAGIBQRX-HRCADAONSA-N Arg-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O LXMKTIZAGIBQRX-HRCADAONSA-N 0.000 description 9
- MOGMYRUNTKYZFB-UNQGMJICSA-N Arg-Thr-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MOGMYRUNTKYZFB-UNQGMJICSA-N 0.000 description 9
- QTAIIXQCOPUNBQ-QXEWZRGKSA-N Arg-Val-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QTAIIXQCOPUNBQ-QXEWZRGKSA-N 0.000 description 9
- DAPLJWATMAXPPZ-CIUDSAMLSA-N Asn-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(N)=O DAPLJWATMAXPPZ-CIUDSAMLSA-N 0.000 description 9
- UGXVKHRDGLYFKR-CIUDSAMLSA-N Asn-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O UGXVKHRDGLYFKR-CIUDSAMLSA-N 0.000 description 9
- CZIXHXIJJZLYRJ-SRVKXCTJSA-N Asn-Cys-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CZIXHXIJJZLYRJ-SRVKXCTJSA-N 0.000 description 9
- OOWSBIOUKIUWLO-RCOVLWMOSA-N Asn-Gly-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O OOWSBIOUKIUWLO-RCOVLWMOSA-N 0.000 description 9
- ANPFQTJEPONRPL-UGYAYLCHSA-N Asn-Ile-Asp Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O ANPFQTJEPONRPL-UGYAYLCHSA-N 0.000 description 9
- UHGUKCOQUNPSKK-CIUDSAMLSA-N Asn-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N UHGUKCOQUNPSKK-CIUDSAMLSA-N 0.000 description 9
- FHETWELNCBMRMG-HJGDQZAQSA-N Asn-Leu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FHETWELNCBMRMG-HJGDQZAQSA-N 0.000 description 9
- OROMFUQQTSWUTI-IHRRRGAJSA-N Asn-Phe-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N OROMFUQQTSWUTI-IHRRRGAJSA-N 0.000 description 9
- RBOBTTLFPRSXKZ-BZSNNMDCSA-N Asn-Phe-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RBOBTTLFPRSXKZ-BZSNNMDCSA-N 0.000 description 9
- HPNDKUOLNRVRAY-BIIVOSGPSA-N Asn-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N)C(=O)O HPNDKUOLNRVRAY-BIIVOSGPSA-N 0.000 description 9
- BCADFFUQHIMQAA-KKHAAJSZSA-N Asn-Thr-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BCADFFUQHIMQAA-KKHAAJSZSA-N 0.000 description 9
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 9
- HBUJSDCLZCXXCW-YDHLFZDLSA-N Asn-Val-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HBUJSDCLZCXXCW-YDHLFZDLSA-N 0.000 description 9
- FTNVLGCFIJEMQT-CIUDSAMLSA-N Asp-Cys-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N FTNVLGCFIJEMQT-CIUDSAMLSA-N 0.000 description 9
- DZQKLNLLWFQONU-LKXGYXEUSA-N Asp-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(=O)O)N)O DZQKLNLLWFQONU-LKXGYXEUSA-N 0.000 description 9
- PZXPWHFYZXTFBI-YUMQZZPRSA-N Asp-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PZXPWHFYZXTFBI-YUMQZZPRSA-N 0.000 description 9
- SPKCGKRUYKMDHP-GUDRVLHUSA-N Asp-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N SPKCGKRUYKMDHP-GUDRVLHUSA-N 0.000 description 9
- SPWXXPFDTMYTRI-IUKAMOBKSA-N Asp-Ile-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SPWXXPFDTMYTRI-IUKAMOBKSA-N 0.000 description 9
- AYFVRYXNDHBECD-YUMQZZPRSA-N Asp-Leu-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AYFVRYXNDHBECD-YUMQZZPRSA-N 0.000 description 9
- UJGRZQYSNYTCAX-SRVKXCTJSA-N Asp-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UJGRZQYSNYTCAX-SRVKXCTJSA-N 0.000 description 9
- XWSIYTYNLKCLJB-CIUDSAMLSA-N Asp-Lys-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O XWSIYTYNLKCLJB-CIUDSAMLSA-N 0.000 description 9
- RXBGWGRSWXOBGK-KKUMJFAQSA-N Asp-Lys-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O RXBGWGRSWXOBGK-KKUMJFAQSA-N 0.000 description 9
- VNXQRBXEQXLERQ-CIUDSAMLSA-N Asp-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N VNXQRBXEQXLERQ-CIUDSAMLSA-N 0.000 description 9
- NJLLRXWFPQQPHV-SRVKXCTJSA-N Asp-Tyr-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O NJLLRXWFPQQPHV-SRVKXCTJSA-N 0.000 description 9
- PLOKOIJSGCISHE-BYULHYEWSA-N Asp-Val-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PLOKOIJSGCISHE-BYULHYEWSA-N 0.000 description 9
- WXKWQSDHEXKKNC-ZKWXMUAHSA-N Cys-Asp-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N WXKWQSDHEXKKNC-ZKWXMUAHSA-N 0.000 description 9
- ATPDEYTYWVMINF-ZLUOBGJFSA-N Cys-Cys-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O ATPDEYTYWVMINF-ZLUOBGJFSA-N 0.000 description 9
- GUKYYUFHWYRMEU-WHFBIAKZSA-N Cys-Gly-Asp Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O GUKYYUFHWYRMEU-WHFBIAKZSA-N 0.000 description 9
- SKSJPIBFNFPTJB-NKWVEPMBSA-N Cys-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CS)N)C(=O)O SKSJPIBFNFPTJB-NKWVEPMBSA-N 0.000 description 9
- UCSXXFRXHGUXCQ-SRVKXCTJSA-N Cys-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CS)N UCSXXFRXHGUXCQ-SRVKXCTJSA-N 0.000 description 9
- QQOWCDCBFFBRQH-IXOXFDKPSA-N Cys-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CS)N)O QQOWCDCBFFBRQH-IXOXFDKPSA-N 0.000 description 9
- KVCJEMHFLGVINV-ZLUOBGJFSA-N Cys-Ser-Asn Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(N)=O KVCJEMHFLGVINV-ZLUOBGJFSA-N 0.000 description 9
- JRZMCSIUYGSJKP-ZKWXMUAHSA-N Cys-Val-Asn Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O JRZMCSIUYGSJKP-ZKWXMUAHSA-N 0.000 description 9
- 241001533413 Deltavirus Species 0.000 description 9
- HHWQMFIGMMOVFK-WDSKDSINSA-N Gln-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O HHWQMFIGMMOVFK-WDSKDSINSA-N 0.000 description 9
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 9
- INFBPLSHYFALDE-ACZMJKKPSA-N Gln-Asn-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O INFBPLSHYFALDE-ACZMJKKPSA-N 0.000 description 9
- LMPBBFWHCRURJD-LAEOZQHASA-N Gln-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)N)N LMPBBFWHCRURJD-LAEOZQHASA-N 0.000 description 9
- WLODHVXYKYHLJD-ACZMJKKPSA-N Gln-Asp-Ser Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N WLODHVXYKYHLJD-ACZMJKKPSA-N 0.000 description 9
- PNENQZWRFMUZOM-DCAQKATOSA-N Gln-Glu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O PNENQZWRFMUZOM-DCAQKATOSA-N 0.000 description 9
- XKBASPWPBXNVLQ-WDSKDSINSA-N Gln-Gly-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XKBASPWPBXNVLQ-WDSKDSINSA-N 0.000 description 9
- VGTDBGYFVWOQTI-RYUDHWBXSA-N Gln-Gly-Phe Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VGTDBGYFVWOQTI-RYUDHWBXSA-N 0.000 description 9
- FTIJVMLAGRAYMJ-MNXVOIDGSA-N Gln-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(N)=O FTIJVMLAGRAYMJ-MNXVOIDGSA-N 0.000 description 9
- VZRAXPGTUNDIDK-GUBZILKMSA-N Gln-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VZRAXPGTUNDIDK-GUBZILKMSA-N 0.000 description 9
- MLSKFHLRFVGNLL-WDCWCFNPSA-N Gln-Leu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MLSKFHLRFVGNLL-WDCWCFNPSA-N 0.000 description 9
- HPCOBEHVEHWREJ-DCAQKATOSA-N Gln-Lys-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O HPCOBEHVEHWREJ-DCAQKATOSA-N 0.000 description 9
- QBEWLBKBGXVVPD-RYUDHWBXSA-N Gln-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCC(=O)N)N QBEWLBKBGXVVPD-RYUDHWBXSA-N 0.000 description 9
- DCWNCMRZIZSZBL-KKUMJFAQSA-N Gln-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O DCWNCMRZIZSZBL-KKUMJFAQSA-N 0.000 description 9
- KUBFPYIMAGXGBT-ACZMJKKPSA-N Gln-Ser-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KUBFPYIMAGXGBT-ACZMJKKPSA-N 0.000 description 9
- GHAXJVNBAKGWEJ-AVGNSLFASA-N Gln-Ser-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O GHAXJVNBAKGWEJ-AVGNSLFASA-N 0.000 description 9
- DYVMTEWCGAVKSE-HJGDQZAQSA-N Gln-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O DYVMTEWCGAVKSE-HJGDQZAQSA-N 0.000 description 9
- ARYKRXHBIPLULY-XKBZYTNZSA-N Gln-Thr-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ARYKRXHBIPLULY-XKBZYTNZSA-N 0.000 description 9
- DIXKFOPPGWKZLY-CIUDSAMLSA-N Glu-Arg-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O DIXKFOPPGWKZLY-CIUDSAMLSA-N 0.000 description 9
- JPHYJQHPILOKHC-ACZMJKKPSA-N Glu-Asp-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JPHYJQHPILOKHC-ACZMJKKPSA-N 0.000 description 9
- FKGNJUCQKXQNRA-NRPADANISA-N Glu-Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O FKGNJUCQKXQNRA-NRPADANISA-N 0.000 description 9
- HUFCEIHAFNVSNR-IHRRRGAJSA-N Glu-Gln-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HUFCEIHAFNVSNR-IHRRRGAJSA-N 0.000 description 9
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 9
- KRGZZKWSBGPLKL-IUCAKERBSA-N Glu-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N KRGZZKWSBGPLKL-IUCAKERBSA-N 0.000 description 9
- ZWQVYZXPYSYPJD-RYUDHWBXSA-N Glu-Gly-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZWQVYZXPYSYPJD-RYUDHWBXSA-N 0.000 description 9
- QXDXIXFSFHUYAX-MNXVOIDGSA-N Glu-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCC(O)=O QXDXIXFSFHUYAX-MNXVOIDGSA-N 0.000 description 9
- KRRFFAHEAOCBCQ-SIUGBPQLSA-N Glu-Ile-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KRRFFAHEAOCBCQ-SIUGBPQLSA-N 0.000 description 9
- PJBVXVBTTFZPHJ-GUBZILKMSA-N Glu-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)O)N PJBVXVBTTFZPHJ-GUBZILKMSA-N 0.000 description 9
- MWMJCGBSIORNCD-AVGNSLFASA-N Glu-Leu-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O MWMJCGBSIORNCD-AVGNSLFASA-N 0.000 description 9
- LKOAAMXDJGEYMS-ZPFDUUQYSA-N Glu-Met-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LKOAAMXDJGEYMS-ZPFDUUQYSA-N 0.000 description 9
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 9
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 9
- IDEODOAVGCMUQV-GUBZILKMSA-N Glu-Ser-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IDEODOAVGCMUQV-GUBZILKMSA-N 0.000 description 9
- YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 description 9
- QSTLUOIOYLYLLF-WDSKDSINSA-N Gly-Asp-Glu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QSTLUOIOYLYLLF-WDSKDSINSA-N 0.000 description 9
- NMROINAYXCACKF-WHFBIAKZSA-N Gly-Cys-Cys Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O NMROINAYXCACKF-WHFBIAKZSA-N 0.000 description 9
- NPSWCZIRBAYNSB-JHEQGTHGSA-N Gly-Gln-Thr Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O NPSWCZIRBAYNSB-JHEQGTHGSA-N 0.000 description 9
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 9
- SWQALSGKVLYKDT-ZKWXMUAHSA-N Gly-Ile-Ala Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SWQALSGKVLYKDT-ZKWXMUAHSA-N 0.000 description 9
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 9
- LUJVWKKYHSLULQ-ZKWXMUAHSA-N Gly-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN LUJVWKKYHSLULQ-ZKWXMUAHSA-N 0.000 description 9
- XVYKMNXXJXQKME-XEGUGMAKSA-N Gly-Ile-Tyr Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XVYKMNXXJXQKME-XEGUGMAKSA-N 0.000 description 9
- PTIIBFKSLCYQBO-NHCYSSNCSA-N Gly-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CN PTIIBFKSLCYQBO-NHCYSSNCSA-N 0.000 description 9
- CVFOYJJOZYYEPE-KBPBESRZSA-N Gly-Lys-Tyr Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CVFOYJJOZYYEPE-KBPBESRZSA-N 0.000 description 9
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 9
- RHRLHXQWHCNJKR-PMVVWTBXSA-N Gly-Thr-His Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 RHRLHXQWHCNJKR-PMVVWTBXSA-N 0.000 description 9
- UMBDRSMLCUYIRI-DVJZZOLTSA-N Gly-Trp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN)O UMBDRSMLCUYIRI-DVJZZOLTSA-N 0.000 description 9
- OCRQUYDOYKCOQG-IRXDYDNUSA-N Gly-Tyr-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 OCRQUYDOYKCOQG-IRXDYDNUSA-N 0.000 description 9
- BNMRSWQOHIQTFL-JSGCOSHPSA-N Gly-Val-Phe Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 BNMRSWQOHIQTFL-JSGCOSHPSA-N 0.000 description 9
- SBVMXEZQJVUARN-XPUUQOCRSA-N Gly-Val-Ser Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O SBVMXEZQJVUARN-XPUUQOCRSA-N 0.000 description 9
- KZTLOHBDLMIFSH-XVYDVKMFSA-N His-Ala-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O KZTLOHBDLMIFSH-XVYDVKMFSA-N 0.000 description 9
- HTZKFIYQMHJWSQ-INTQDDNPSA-N His-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N HTZKFIYQMHJWSQ-INTQDDNPSA-N 0.000 description 9
- MJUUWJJEUOBDGW-IHRRRGAJSA-N His-Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 MJUUWJJEUOBDGW-IHRRRGAJSA-N 0.000 description 9
- UWSMZKRTOZEGDD-CUJWVEQBSA-N His-Thr-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O UWSMZKRTOZEGDD-CUJWVEQBSA-N 0.000 description 9
- RGSOCXHDOPQREB-ZPFDUUQYSA-N Ile-Asp-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N RGSOCXHDOPQREB-ZPFDUUQYSA-N 0.000 description 9
- LLHYWBGDMBGNHA-VGDYDELISA-N Ile-Cys-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N LLHYWBGDMBGNHA-VGDYDELISA-N 0.000 description 9
- NZOCIWKZUVUNDW-ZKWXMUAHSA-N Ile-Gly-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O NZOCIWKZUVUNDW-ZKWXMUAHSA-N 0.000 description 9
- MQFGXJNSUJTXDT-QSFUFRPTSA-N Ile-Gly-Ile Chemical compound N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)O MQFGXJNSUJTXDT-QSFUFRPTSA-N 0.000 description 9
- VOBYAKCXGQQFLR-LSJOCFKGSA-N Ile-Gly-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O VOBYAKCXGQQFLR-LSJOCFKGSA-N 0.000 description 9
- WIZPFZKOFZXDQG-HTFCKZLJSA-N Ile-Ile-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O WIZPFZKOFZXDQG-HTFCKZLJSA-N 0.000 description 9
- AXNGDPAKKCEKGY-QPHKQPEJSA-N Ile-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N AXNGDPAKKCEKGY-QPHKQPEJSA-N 0.000 description 9
- GVKKVHNRTUFCCE-BJDJZHNGSA-N Ile-Leu-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)O)N GVKKVHNRTUFCCE-BJDJZHNGSA-N 0.000 description 9
- PXKACEXYLPBMAD-JBDRJPRFSA-N Ile-Ser-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PXKACEXYLPBMAD-JBDRJPRFSA-N 0.000 description 9
- RQJUKVXWAKJDBW-SVSWQMSJSA-N Ile-Ser-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N RQJUKVXWAKJDBW-SVSWQMSJSA-N 0.000 description 9
- YCKPUHHMCFSUMD-IUKAMOBKSA-N Ile-Thr-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N YCKPUHHMCFSUMD-IUKAMOBKSA-N 0.000 description 9
- ZUWSVOYKBCHLRR-MGHWNKPDSA-N Ile-Tyr-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZUWSVOYKBCHLRR-MGHWNKPDSA-N 0.000 description 9
- HASRFYOMVPJRPU-SRVKXCTJSA-N Leu-Arg-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O HASRFYOMVPJRPU-SRVKXCTJSA-N 0.000 description 9
- KKXDHFKZWKLYGB-GUBZILKMSA-N Leu-Asn-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKXDHFKZWKLYGB-GUBZILKMSA-N 0.000 description 9
- GZAUZBUKDXYPEH-CIUDSAMLSA-N Leu-Cys-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)O)N GZAUZBUKDXYPEH-CIUDSAMLSA-N 0.000 description 9
- ZYLJULGXQDNXDK-GUBZILKMSA-N Leu-Gln-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ZYLJULGXQDNXDK-GUBZILKMSA-N 0.000 description 9
- CQGSYZCULZMEDE-SRVKXCTJSA-N Leu-Gln-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CQGSYZCULZMEDE-SRVKXCTJSA-N 0.000 description 9
- FIYMBBHGYNQFOP-IUCAKERBSA-N Leu-Gly-Gln Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N FIYMBBHGYNQFOP-IUCAKERBSA-N 0.000 description 9
- POZULHZYLPGXMR-ONGXEEELSA-N Leu-Gly-Val Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O POZULHZYLPGXMR-ONGXEEELSA-N 0.000 description 9
- SGIIOQQGLUUMDQ-IHRRRGAJSA-N Leu-His-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N SGIIOQQGLUUMDQ-IHRRRGAJSA-N 0.000 description 9
- AVEGDIAXTDVBJS-XUXIUFHCSA-N Leu-Ile-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AVEGDIAXTDVBJS-XUXIUFHCSA-N 0.000 description 9
- ORWTWZXGDBYVCP-BJDJZHNGSA-N Leu-Ile-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(C)C ORWTWZXGDBYVCP-BJDJZHNGSA-N 0.000 description 9
- QJXHMYMRGDOHRU-NHCYSSNCSA-N Leu-Ile-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O QJXHMYMRGDOHRU-NHCYSSNCSA-N 0.000 description 9
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 9
- LXKNSJLSGPNHSK-KKUMJFAQSA-N Leu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N LXKNSJLSGPNHSK-KKUMJFAQSA-N 0.000 description 9
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 9
- JDBQSGMJBMPNFT-AVGNSLFASA-N Leu-Pro-Val Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O JDBQSGMJBMPNFT-AVGNSLFASA-N 0.000 description 9
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-N 0.000 description 9
- IWMJFLJQHIDZQW-KKUMJFAQSA-N Leu-Ser-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IWMJFLJQHIDZQW-KKUMJFAQSA-N 0.000 description 9
- ICYRCNICGBJLGM-HJGDQZAQSA-N Leu-Thr-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O ICYRCNICGBJLGM-HJGDQZAQSA-N 0.000 description 9
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 9
- UCRJTSIIAYHOHE-ULQDDVLXSA-N Leu-Tyr-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UCRJTSIIAYHOHE-ULQDDVLXSA-N 0.000 description 9
- FBNPMTNBFFAMMH-AVGNSLFASA-N Leu-Val-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-AVGNSLFASA-N 0.000 description 9
- VHNOAIFVYUQOOY-XUXIUFHCSA-N Lys-Arg-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VHNOAIFVYUQOOY-XUXIUFHCSA-N 0.000 description 9
- ZQCVMVCVPFYXHZ-SRVKXCTJSA-N Lys-Asn-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCCN ZQCVMVCVPFYXHZ-SRVKXCTJSA-N 0.000 description 9
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 9
- DZQYZKPINJLLEN-KKUMJFAQSA-N Lys-Cys-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N)O DZQYZKPINJLLEN-KKUMJFAQSA-N 0.000 description 9
- RZHLIPMZXOEJTL-AVGNSLFASA-N Lys-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N RZHLIPMZXOEJTL-AVGNSLFASA-N 0.000 description 9
- NNKLKUUGESXCBS-KBPBESRZSA-N Lys-Gly-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NNKLKUUGESXCBS-KBPBESRZSA-N 0.000 description 9
- SLQJJFAVWSZLBL-BJDJZHNGSA-N Lys-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN SLQJJFAVWSZLBL-BJDJZHNGSA-N 0.000 description 9
- XREQQOATSMMAJP-MGHWNKPDSA-N Lys-Ile-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XREQQOATSMMAJP-MGHWNKPDSA-N 0.000 description 9
- ATNKHRAIZCMCCN-BZSNNMDCSA-N Lys-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)N ATNKHRAIZCMCCN-BZSNNMDCSA-N 0.000 description 9
- JYVCOTWSRGFABJ-DCAQKATOSA-N Lys-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N JYVCOTWSRGFABJ-DCAQKATOSA-N 0.000 description 9
- MIFFFXHMAHFACR-KATARQTJSA-N Lys-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCCCN MIFFFXHMAHFACR-KATARQTJSA-N 0.000 description 9
- RMOKGALPSPOYKE-KATARQTJSA-N Lys-Thr-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMOKGALPSPOYKE-KATARQTJSA-N 0.000 description 9
- OSOLWRWQADPDIQ-DCAQKATOSA-N Met-Asp-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OSOLWRWQADPDIQ-DCAQKATOSA-N 0.000 description 9
- KLFPZIUIXZNEKY-DCAQKATOSA-N Met-Gln-Met Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O KLFPZIUIXZNEKY-DCAQKATOSA-N 0.000 description 9
- GWADARYJIJDYRC-XGEHTFHBSA-N Met-Thr-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O GWADARYJIJDYRC-XGEHTFHBSA-N 0.000 description 9
- LIIXIZKVWNYQHB-STECZYCISA-N Met-Tyr-Ile Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LIIXIZKVWNYQHB-STECZYCISA-N 0.000 description 9
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 9
- AUEJLPRZGVVDNU-UHFFFAOYSA-N N-L-tyrosyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CC1=CC=C(O)C=C1 AUEJLPRZGVVDNU-UHFFFAOYSA-N 0.000 description 9
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 9
- KAHUBGWSIQNZQQ-KKUMJFAQSA-N Phe-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 KAHUBGWSIQNZQQ-KKUMJFAQSA-N 0.000 description 9
- AWAYOWOUGVZXOB-BZSNNMDCSA-N Phe-Asn-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 AWAYOWOUGVZXOB-BZSNNMDCSA-N 0.000 description 9
- ALHULIGNEXGFRM-QWRGUYRKSA-N Phe-Cys-Gly Chemical compound OC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)CC1=CC=CC=C1 ALHULIGNEXGFRM-QWRGUYRKSA-N 0.000 description 9
- PSBJZLMFFTULDX-IXOXFDKPSA-N Phe-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=CC=C1)N)O PSBJZLMFFTULDX-IXOXFDKPSA-N 0.000 description 9
- IDUCUXTUHHIQIP-SOUVJXGZSA-N Phe-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O IDUCUXTUHHIQIP-SOUVJXGZSA-N 0.000 description 9
- JJHVFCUWLSKADD-ONGXEEELSA-N Phe-Gly-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](C)C(O)=O JJHVFCUWLSKADD-ONGXEEELSA-N 0.000 description 9
- KRYSMKKRRRWOCZ-QEWYBTABSA-N Phe-Ile-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KRYSMKKRRRWOCZ-QEWYBTABSA-N 0.000 description 9
- WEMYTDDMDBLPMI-DKIMLUQUSA-N Phe-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N WEMYTDDMDBLPMI-DKIMLUQUSA-N 0.000 description 9
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 9
- BSKMOCNNLNDIMU-CDMKHQONSA-N Phe-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O BSKMOCNNLNDIMU-CDMKHQONSA-N 0.000 description 9
- FGWUALWGCZJQDJ-URLPEUOOSA-N Phe-Thr-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGWUALWGCZJQDJ-URLPEUOOSA-N 0.000 description 9
- YFXXRYFWJFQAFW-JHYOHUSXSA-N Phe-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N)O YFXXRYFWJFQAFW-JHYOHUSXSA-N 0.000 description 9
- AJLVKXCNXIJHDV-CIUDSAMLSA-N Pro-Ala-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O AJLVKXCNXIJHDV-CIUDSAMLSA-N 0.000 description 9
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 9
- ILMLVTGTUJPQFP-FXQIFTODSA-N Pro-Asp-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ILMLVTGTUJPQFP-FXQIFTODSA-N 0.000 description 9
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 9
- XUSDDSLCRPUKLP-QXEWZRGKSA-N Pro-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 XUSDDSLCRPUKLP-QXEWZRGKSA-N 0.000 description 9
- HQVPQXMCQKXARZ-FXQIFTODSA-N Pro-Cys-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O HQVPQXMCQKXARZ-FXQIFTODSA-N 0.000 description 9
- LHALYDBUDCWMDY-CIUDSAMLSA-N Pro-Glu-Ala Chemical compound C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O LHALYDBUDCWMDY-CIUDSAMLSA-N 0.000 description 9
- VWXGFAIZUQBBBG-UWVGGRQHSA-N Pro-His-Gly Chemical compound C([C@@H](C(=O)NCC(=O)[O-])NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 VWXGFAIZUQBBBG-UWVGGRQHSA-N 0.000 description 9
- BBFRBZYKHIKFBX-GMOBBJLQSA-N Pro-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@@H]1CCCN1 BBFRBZYKHIKFBX-GMOBBJLQSA-N 0.000 description 9
- SUENWIFTSTWUKD-AVGNSLFASA-N Pro-Leu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O SUENWIFTSTWUKD-AVGNSLFASA-N 0.000 description 9
- ZUZINZIJHJFJRN-UBHSHLNASA-N Pro-Phe-Ala Chemical compound C([C@@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 ZUZINZIJHJFJRN-UBHSHLNASA-N 0.000 description 9
- MLKVIVZCFYRTIR-KKUMJFAQSA-N Pro-Phe-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O MLKVIVZCFYRTIR-KKUMJFAQSA-N 0.000 description 9
- AJBQTGZIZQXBLT-STQMWFEESA-N Pro-Phe-Gly Chemical compound C([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 AJBQTGZIZQXBLT-STQMWFEESA-N 0.000 description 9
- DWPXHLIBFQLKLK-CYDGBPFRSA-N Pro-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 DWPXHLIBFQLKLK-CYDGBPFRSA-N 0.000 description 9
- CNUIHOAISPKQPY-HSHDSVGOSA-N Pro-Thr-Trp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O CNUIHOAISPKQPY-HSHDSVGOSA-N 0.000 description 9
- WTWGOQRNRFHFQD-JBDRJPRFSA-N Ser-Ala-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WTWGOQRNRFHFQD-JBDRJPRFSA-N 0.000 description 9
- UCXDHBORXLVBNC-ZLUOBGJFSA-N Ser-Asn-Cys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(O)=O UCXDHBORXLVBNC-ZLUOBGJFSA-N 0.000 description 9
- BCKYYTVFBXHPOG-ACZMJKKPSA-N Ser-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)N BCKYYTVFBXHPOG-ACZMJKKPSA-N 0.000 description 9
- RNFKSBPHLTZHLU-WHFBIAKZSA-N Ser-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)O RNFKSBPHLTZHLU-WHFBIAKZSA-N 0.000 description 9
- FMDHKPRACUXATF-ACZMJKKPSA-N Ser-Gln-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O FMDHKPRACUXATF-ACZMJKKPSA-N 0.000 description 9
- UFKPDBLKLOBMRH-XHNCKOQMSA-N Ser-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)C(=O)O UFKPDBLKLOBMRH-XHNCKOQMSA-N 0.000 description 9
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 9
- CXBFHZLODKPIJY-AAEUAGOBSA-N Ser-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N CXBFHZLODKPIJY-AAEUAGOBSA-N 0.000 description 9
- XNCUYZKGQOCOQH-YUMQZZPRSA-N Ser-Leu-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O XNCUYZKGQOCOQH-YUMQZZPRSA-N 0.000 description 9
- NNFMANHDYSVNIO-DCAQKATOSA-N Ser-Lys-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NNFMANHDYSVNIO-DCAQKATOSA-N 0.000 description 9
- SRKMDKACHDVPMD-SRVKXCTJSA-N Ser-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N SRKMDKACHDVPMD-SRVKXCTJSA-N 0.000 description 9
- PTWIYDNFWPXQSD-GARJFASQSA-N Ser-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N)C(=O)O PTWIYDNFWPXQSD-GARJFASQSA-N 0.000 description 9
- RXSWQCATLWVDLI-XGEHTFHBSA-N Ser-Met-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RXSWQCATLWVDLI-XGEHTFHBSA-N 0.000 description 9
- XVWDJUROVRQKAE-KKUMJFAQSA-N Ser-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CC1=CC=CC=C1 XVWDJUROVRQKAE-KKUMJFAQSA-N 0.000 description 9
- RWDVVSKYZBNDCO-MELADBBJSA-N Ser-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CO)N)C(=O)O RWDVVSKYZBNDCO-MELADBBJSA-N 0.000 description 9
- FBLNYDYPCLFTSP-IXOXFDKPSA-N Ser-Phe-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FBLNYDYPCLFTSP-IXOXFDKPSA-N 0.000 description 9
- HHJFMHQYEAAOBM-ZLUOBGJFSA-N Ser-Ser-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O HHJFMHQYEAAOBM-ZLUOBGJFSA-N 0.000 description 9
- WLJPJRGQRNCIQS-ZLUOBGJFSA-N Ser-Ser-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O WLJPJRGQRNCIQS-ZLUOBGJFSA-N 0.000 description 9
- KKKVOZNCLALMPV-XKBZYTNZSA-N Ser-Thr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KKKVOZNCLALMPV-XKBZYTNZSA-N 0.000 description 9
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 9
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 9
- VEVYMLNYMULSMS-AVGNSLFASA-N Ser-Tyr-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEVYMLNYMULSMS-AVGNSLFASA-N 0.000 description 9
- MFQMZDPAZRZAPV-NAKRPEOUSA-N Ser-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)N MFQMZDPAZRZAPV-NAKRPEOUSA-N 0.000 description 9
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 9
- ODRUTDLAONAVDV-IHRRRGAJSA-N Ser-Val-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ODRUTDLAONAVDV-IHRRRGAJSA-N 0.000 description 9
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 9
- TZKPNGDGUVREEB-FOHZUACHSA-N Thr-Asn-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O TZKPNGDGUVREEB-FOHZUACHSA-N 0.000 description 9
- PQLXHSACXPGWPD-GSSVUCPTSA-N Thr-Asn-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PQLXHSACXPGWPD-GSSVUCPTSA-N 0.000 description 9
- LMMDEZPNUTZJAY-GCJQMDKQSA-N Thr-Asp-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O LMMDEZPNUTZJAY-GCJQMDKQSA-N 0.000 description 9
- MFEBUIFJVPNZLO-OLHMAJIHSA-N Thr-Asp-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O MFEBUIFJVPNZLO-OLHMAJIHSA-N 0.000 description 9
- QILPDQCTQZDHFM-HJGDQZAQSA-N Thr-Gln-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QILPDQCTQZDHFM-HJGDQZAQSA-N 0.000 description 9
- ZQUKYJOKQBRBCS-GLLZPBPUSA-N Thr-Gln-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O ZQUKYJOKQBRBCS-GLLZPBPUSA-N 0.000 description 9
- VUVCRYXYUUPGSB-GLLZPBPUSA-N Thr-Gln-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N)O VUVCRYXYUUPGSB-GLLZPBPUSA-N 0.000 description 9
- KGKWKSSSQGGYAU-SUSMZKCASA-N Thr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KGKWKSSSQGGYAU-SUSMZKCASA-N 0.000 description 9
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 9
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 9
- KZSYAEWQMJEGRZ-RHYQMDGZSA-N Thr-Leu-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O KZSYAEWQMJEGRZ-RHYQMDGZSA-N 0.000 description 9
- HPQHHRLWSAMMKG-KATARQTJSA-N Thr-Lys-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N)O HPQHHRLWSAMMKG-KATARQTJSA-N 0.000 description 9
- SPVHQURZJCUDQC-VOAKCMCISA-N Thr-Lys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O SPVHQURZJCUDQC-VOAKCMCISA-N 0.000 description 9
- NZRUWPIYECBYRK-HTUGSXCWSA-N Thr-Phe-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O NZRUWPIYECBYRK-HTUGSXCWSA-N 0.000 description 9
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 9
- NWECYMJLJGCBOD-UNQGMJICSA-N Thr-Phe-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O NWECYMJLJGCBOD-UNQGMJICSA-N 0.000 description 9
- MXDOAJQRJBMGMO-FJXKBIBVSA-N Thr-Pro-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O MXDOAJQRJBMGMO-FJXKBIBVSA-N 0.000 description 9
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 9
- KVEWWQRTAVMOFT-KJEVXHAQSA-N Thr-Tyr-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O KVEWWQRTAVMOFT-KJEVXHAQSA-N 0.000 description 9
- IBBBOLAPFHRDHW-BPUTZDHNSA-N Trp-Asn-Arg Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N IBBBOLAPFHRDHW-BPUTZDHNSA-N 0.000 description 9
- UKINEYBQXPMOJO-UBHSHLNASA-N Trp-Asn-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N UKINEYBQXPMOJO-UBHSHLNASA-N 0.000 description 9
- UQHPXCFAHVTWFU-BVSLBCMMSA-N Trp-Phe-Val Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O UQHPXCFAHVTWFU-BVSLBCMMSA-N 0.000 description 9
- PEVVXUGSAKEPEN-AVGNSLFASA-N Tyr-Asn-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PEVVXUGSAKEPEN-AVGNSLFASA-N 0.000 description 9
- SCCKSNREWHMKOJ-SRVKXCTJSA-N Tyr-Asn-Ser Chemical compound N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O SCCKSNREWHMKOJ-SRVKXCTJSA-N 0.000 description 9
- NSTPFWRAIDTNGH-BZSNNMDCSA-N Tyr-Asn-Tyr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NSTPFWRAIDTNGH-BZSNNMDCSA-N 0.000 description 9
- NRFTYDWKWGJLAR-MELADBBJSA-N Tyr-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O NRFTYDWKWGJLAR-MELADBBJSA-N 0.000 description 9
- IWRMTNJCCMEBEX-AVGNSLFASA-N Tyr-Glu-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O IWRMTNJCCMEBEX-AVGNSLFASA-N 0.000 description 9
- AZGZDDNKFFUDEH-QWRGUYRKSA-N Tyr-Gly-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AZGZDDNKFFUDEH-QWRGUYRKSA-N 0.000 description 9
- FMXFHNSFABRVFZ-BZSNNMDCSA-N Tyr-Lys-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O FMXFHNSFABRVFZ-BZSNNMDCSA-N 0.000 description 9
- TYFLVOUZHQUBGM-IHRRRGAJSA-N Tyr-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TYFLVOUZHQUBGM-IHRRRGAJSA-N 0.000 description 9
- XFEMMSGONWQACR-KJEVXHAQSA-N Tyr-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O XFEMMSGONWQACR-KJEVXHAQSA-N 0.000 description 9
- RVGVIWNHABGIFH-IHRRRGAJSA-N Tyr-Val-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O RVGVIWNHABGIFH-IHRRRGAJSA-N 0.000 description 9
- FZSPNKUFROZBSG-ZKWXMUAHSA-N Val-Ala-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O FZSPNKUFROZBSG-ZKWXMUAHSA-N 0.000 description 9
- RUCNAYOMFXRIKJ-DCAQKATOSA-N Val-Ala-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN RUCNAYOMFXRIKJ-DCAQKATOSA-N 0.000 description 9
- JIODCDXKCJRMEH-NHCYSSNCSA-N Val-Arg-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N JIODCDXKCJRMEH-NHCYSSNCSA-N 0.000 description 9
- LIQJSDDOULTANC-QSFUFRPTSA-N Val-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N LIQJSDDOULTANC-QSFUFRPTSA-N 0.000 description 9
- KXUKIBHIVRYOIP-ZKWXMUAHSA-N Val-Asp-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N KXUKIBHIVRYOIP-ZKWXMUAHSA-N 0.000 description 9
- VLDMQVZZWDOKQF-AUTRQRHGSA-N Val-Glu-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VLDMQVZZWDOKQF-AUTRQRHGSA-N 0.000 description 9
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 9
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 9
- BVWPHWLFGRCECJ-JSGCOSHPSA-N Val-Gly-Tyr Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N BVWPHWLFGRCECJ-JSGCOSHPSA-N 0.000 description 9
- CPGJELLYDQEDRK-NAKRPEOUSA-N Val-Ile-Ala Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](C)C(O)=O CPGJELLYDQEDRK-NAKRPEOUSA-N 0.000 description 9
- KDKLLPMFFGYQJD-CYDGBPFRSA-N Val-Ile-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N KDKLLPMFFGYQJD-CYDGBPFRSA-N 0.000 description 9
- UKEVLVBHRKWECS-LSJOCFKGSA-N Val-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](C(C)C)N UKEVLVBHRKWECS-LSJOCFKGSA-N 0.000 description 9
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 9
- LJSZPMSUYKKKCP-UBHSHLNASA-N Val-Phe-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 LJSZPMSUYKKKCP-UBHSHLNASA-N 0.000 description 9
- MHHAWNPHDLCPLF-ULQDDVLXSA-N Val-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=CC=C1 MHHAWNPHDLCPLF-ULQDDVLXSA-N 0.000 description 9
- UQMPYVLTQCGRSK-IFFSRLJSSA-N Val-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N)O UQMPYVLTQCGRSK-IFFSRLJSSA-N 0.000 description 9
- LCHZBEUVGAVMKS-RHYQMDGZSA-N Val-Thr-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(O)=O LCHZBEUVGAVMKS-RHYQMDGZSA-N 0.000 description 9
- XNLUVJPMPAZHCY-JYJNAYRXSA-N Val-Val-Phe Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 XNLUVJPMPAZHCY-JYJNAYRXSA-N 0.000 description 9
- 108010087924 alanylproline Proteins 0.000 description 9
- 108010059459 arginyl-threonyl-phenylalanine Proteins 0.000 description 9
- 108010062796 arginyllysine Proteins 0.000 description 9
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 9
- 108010047857 aspartylglycine Proteins 0.000 description 9
- 108010078326 glycyl-glycyl-valine Proteins 0.000 description 9
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 9
- 108010078274 isoleucylvaline Proteins 0.000 description 9
- 108010064235 lysylglycine Proteins 0.000 description 9
- 108010038320 lysylphenylalanine Proteins 0.000 description 9
- 108010026333 seryl-proline Proteins 0.000 description 9
- -1 sugars Amino acid Chemical class 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 108010078580 tyrosylleucine Proteins 0.000 description 9
- PCIFXPRIFWKWLK-YUMQZZPRSA-N Ala-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N PCIFXPRIFWKWLK-YUMQZZPRSA-N 0.000 description 8
- YNSCBOUZTAGIGO-ZLUOBGJFSA-N Asn-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N)C(=O)N YNSCBOUZTAGIGO-ZLUOBGJFSA-N 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 8
- IBYOLNARKHMLBG-WHOFXGATSA-N Gly-Phe-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 IBYOLNARKHMLBG-WHOFXGATSA-N 0.000 description 8
- FNXSYBOHALPRHV-ONGXEEELSA-N Gly-Val-Lys Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN FNXSYBOHALPRHV-ONGXEEELSA-N 0.000 description 8
- CEPIAEUVRKGPGP-DSYPUSFNSA-N Ile-Lys-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 CEPIAEUVRKGPGP-DSYPUSFNSA-N 0.000 description 8
- RTSQPLLOYSGMKM-DSYPUSFNSA-N Ile-Trp-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)O)N RTSQPLLOYSGMKM-DSYPUSFNSA-N 0.000 description 8
- HMDDEJADNKQTBR-BZSNNMDCSA-N Leu-His-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O HMDDEJADNKQTBR-BZSNNMDCSA-N 0.000 description 8
- DIDLUFMLRUJLFB-FKBYEOEOSA-N Pro-Trp-Tyr Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)O DIDLUFMLRUJLFB-FKBYEOEOSA-N 0.000 description 8
- LCCSEJSPBWKBNT-OSUNSFLBSA-N Thr-Ile-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N LCCSEJSPBWKBNT-OSUNSFLBSA-N 0.000 description 8
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 8
- MJFSRZZJQWZHFQ-SRVKXCTJSA-N Val-Met-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)O)N MJFSRZZJQWZHFQ-SRVKXCTJSA-N 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- ZMUQQMGITUJQTI-CIUDSAMLSA-N Asn-Leu-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O ZMUQQMGITUJQTI-CIUDSAMLSA-N 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- MQJDLNRXBOELJW-KKUMJFAQSA-N Gln-Pro-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O MQJDLNRXBOELJW-KKUMJFAQSA-N 0.000 description 7
- SWRVAQHFBRZVNX-GUBZILKMSA-N Glu-Lys-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SWRVAQHFBRZVNX-GUBZILKMSA-N 0.000 description 7
- GMVCSRBOSIUTFC-FXQIFTODSA-N Glu-Ser-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMVCSRBOSIUTFC-FXQIFTODSA-N 0.000 description 7
- DGKBSGNCMCLDSL-BYULHYEWSA-N Gly-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN DGKBSGNCMCLDSL-BYULHYEWSA-N 0.000 description 7
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- OTCJMMRQBVDQRK-DCAQKATOSA-N Arg-Asp-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OTCJMMRQBVDQRK-DCAQKATOSA-N 0.000 description 6
- NLRJGXZWTKXRHP-DCAQKATOSA-N Asn-Leu-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NLRJGXZWTKXRHP-DCAQKATOSA-N 0.000 description 6
- YXVAESUIQFDBHN-SRVKXCTJSA-N Asn-Phe-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O YXVAESUIQFDBHN-SRVKXCTJSA-N 0.000 description 6
- RGKKALNPOYURGE-ZKWXMUAHSA-N Asp-Ala-Val Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O RGKKALNPOYURGE-ZKWXMUAHSA-N 0.000 description 6
- XXLBHPPXDUWYAG-XQXXSGGOSA-N Gln-Ala-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XXLBHPPXDUWYAG-XQXXSGGOSA-N 0.000 description 6
- ZNTDJIMJKNNSLR-RWRJDSDZSA-N Gln-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZNTDJIMJKNNSLR-RWRJDSDZSA-N 0.000 description 6
- MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 6
- 108010065920 Insulin Lispro Proteins 0.000 description 6
- 241000713666 Lentivirus Species 0.000 description 6
- BMVFXOQHDQZAQU-DCAQKATOSA-N Leu-Pro-Asp Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N BMVFXOQHDQZAQU-DCAQKATOSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 6
- LJUUGSWZPQOJKD-JYJNAYRXSA-N Phe-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O LJUUGSWZPQOJKD-JYJNAYRXSA-N 0.000 description 6
- XYHMFGGWNOFUOU-QXEWZRGKSA-N Pro-Ile-Gly Chemical compound OC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1 XYHMFGGWNOFUOU-QXEWZRGKSA-N 0.000 description 6
- SXJOPONICMGFCR-DCAQKATOSA-N Pro-Ser-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O SXJOPONICMGFCR-DCAQKATOSA-N 0.000 description 6
- UTSWGQNAQRIHAI-UNQGMJICSA-N Thr-Arg-Phe Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 UTSWGQNAQRIHAI-UNQGMJICSA-N 0.000 description 6
- TZVUSFMQWPWHON-NHCYSSNCSA-N Val-Asp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)N TZVUSFMQWPWHON-NHCYSSNCSA-N 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 108010093581 aspartyl-proline Proteins 0.000 description 6
- 210000000170 cell membrane Anatomy 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 108010004073 cysteinylcysteine Proteins 0.000 description 6
- 108010069495 cysteinyltyrosine Proteins 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
- 108010084389 glycyltryptophan Proteins 0.000 description 6
- 108010053037 kyotorphin Proteins 0.000 description 6
- 244000052769 pathogen Species 0.000 description 6
- 229920000575 polymersome Polymers 0.000 description 6
- 108010090894 prolylleucine Proteins 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- FNAJNWPDTIXYJN-CIUDSAMLSA-N Gln-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O FNAJNWPDTIXYJN-CIUDSAMLSA-N 0.000 description 5
- RLZBLVSJDFHDBL-KBIXCLLPSA-N Glu-Ala-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RLZBLVSJDFHDBL-KBIXCLLPSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 241000315672 SARS coronavirus Species 0.000 description 5
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 5
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- QSHGUCSTWRSQAF-FJSLEGQWSA-N s-peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C1=CC=C(OS(O)(=O)=O)C=C1 QSHGUCSTWRSQAF-FJSLEGQWSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- UWMDGPFFTKDUIY-HJGDQZAQSA-N Gln-Pro-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O UWMDGPFFTKDUIY-HJGDQZAQSA-N 0.000 description 4
- SYAYROHMAIHWFB-KBIXCLLPSA-N Glu-Ser-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SYAYROHMAIHWFB-KBIXCLLPSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108010065805 Interleukin-12 Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 229920002873 Polyethylenimine Polymers 0.000 description 4
- 101150010882 S gene Proteins 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000022811 deglycosylation Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000005745 host immune response Effects 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 230000003308 immunostimulating effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 108010080629 tryptophan-leucine Proteins 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- NTUPOKHATNSWCY-PMPSAXMXSA-N (2s)-2-[[(2s)-1-[(2r)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C([C@@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=CC=C1 NTUPOKHATNSWCY-PMPSAXMXSA-N 0.000 description 3
- NWFLONJLUJYCNS-UHFFFAOYSA-N 2-[[2-[[2-[(2-amino-3-phenylpropanoyl)amino]acetyl]amino]acetyl]amino]-3-phenylpropanoic acid Chemical compound C=1C=CC=CC=1CC(C(O)=O)NC(=O)CNC(=O)CNC(=O)C(N)CC1=CC=CC=C1 NWFLONJLUJYCNS-UHFFFAOYSA-N 0.000 description 3
- LBJYAILUMSUTAM-ZLUOBGJFSA-N Ala-Asn-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O LBJYAILUMSUTAM-ZLUOBGJFSA-N 0.000 description 3
- KUDREHRZRIVKHS-UWJYBYFXSA-N Ala-Asp-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KUDREHRZRIVKHS-UWJYBYFXSA-N 0.000 description 3
- LGFCAXJBAZESCF-ACZMJKKPSA-N Ala-Gln-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O LGFCAXJBAZESCF-ACZMJKKPSA-N 0.000 description 3
- YIGLXQRFQVWFEY-NRPADANISA-N Ala-Gln-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O YIGLXQRFQVWFEY-NRPADANISA-N 0.000 description 3
- LMFXXZPPZDCPTA-ZKWXMUAHSA-N Ala-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N LMFXXZPPZDCPTA-ZKWXMUAHSA-N 0.000 description 3
- QHASENCZLDHBGX-ONGXEEELSA-N Ala-Gly-Phe Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QHASENCZLDHBGX-ONGXEEELSA-N 0.000 description 3
- FOHXUHGZZKETFI-JBDRJPRFSA-N Ala-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C)N FOHXUHGZZKETFI-JBDRJPRFSA-N 0.000 description 3
- NMXKFWOEASXOGB-QSFUFRPTSA-N Ala-Ile-His Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 NMXKFWOEASXOGB-QSFUFRPTSA-N 0.000 description 3
- OKIKVSXTXVVFDV-MMWGEVLESA-N Ala-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N OKIKVSXTXVVFDV-MMWGEVLESA-N 0.000 description 3
- VNYMOTCMNHJGTG-JBDRJPRFSA-N Ala-Ile-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O VNYMOTCMNHJGTG-JBDRJPRFSA-N 0.000 description 3
- PVQLRJRPUTXFFX-CIUDSAMLSA-N Ala-Met-Gln Chemical compound CSCC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](CCC(N)=O)C(O)=O PVQLRJRPUTXFFX-CIUDSAMLSA-N 0.000 description 3
- XAXHGSOBFPIRFG-LSJOCFKGSA-N Ala-Pro-His Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O XAXHGSOBFPIRFG-LSJOCFKGSA-N 0.000 description 3
- DYXOFPBJBAHWFY-JBDRJPRFSA-N Ala-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N DYXOFPBJBAHWFY-JBDRJPRFSA-N 0.000 description 3
- SAHQGRZIQVEJPF-JXUBOQSCSA-N Ala-Thr-Lys Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN SAHQGRZIQVEJPF-JXUBOQSCSA-N 0.000 description 3
- XMIAMUXIMWREBJ-HERUPUMHSA-N Ala-Trp-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(=O)N)C(=O)O)N XMIAMUXIMWREBJ-HERUPUMHSA-N 0.000 description 3
- JPOQZCHGOTWRTM-FQPOAREZSA-N Ala-Tyr-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JPOQZCHGOTWRTM-FQPOAREZSA-N 0.000 description 3
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 3
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 3
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 3
- KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 3
- KWTVWJPNHAOREN-IHRRRGAJSA-N Arg-Asn-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KWTVWJPNHAOREN-IHRRRGAJSA-N 0.000 description 3
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- UHFUZWSZQKMDSX-DCAQKATOSA-N Arg-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UHFUZWSZQKMDSX-DCAQKATOSA-N 0.000 description 3
- FSNVAJOPUDVQAR-AVGNSLFASA-N Arg-Lys-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FSNVAJOPUDVQAR-AVGNSLFASA-N 0.000 description 3
- YTMKMRSYXHBGER-IHRRRGAJSA-N Arg-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YTMKMRSYXHBGER-IHRRRGAJSA-N 0.000 description 3
- JPAWCMXVNZPJLO-IHRRRGAJSA-N Arg-Ser-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JPAWCMXVNZPJLO-IHRRRGAJSA-N 0.000 description 3
- LLQIAIUAKGNOSE-NHCYSSNCSA-N Arg-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N LLQIAIUAKGNOSE-NHCYSSNCSA-N 0.000 description 3
- XWGJDUSDTRPQRK-ZLUOBGJFSA-N Asn-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O XWGJDUSDTRPQRK-ZLUOBGJFSA-N 0.000 description 3
- VDCIPFYVCICPEC-FXQIFTODSA-N Asn-Arg-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O VDCIPFYVCICPEC-FXQIFTODSA-N 0.000 description 3
- VKCOHFFSTKCXEQ-OLHMAJIHSA-N Asn-Asn-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VKCOHFFSTKCXEQ-OLHMAJIHSA-N 0.000 description 3
- VWJFQGXPYOPXJH-ZLUOBGJFSA-N Asn-Cys-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)C(=O)N VWJFQGXPYOPXJH-ZLUOBGJFSA-N 0.000 description 3
- AYKKKGFJXIDYLX-ACZMJKKPSA-N Asn-Gln-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O AYKKKGFJXIDYLX-ACZMJKKPSA-N 0.000 description 3
- UBKOVSLDWIHYSY-ACZMJKKPSA-N Asn-Glu-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O UBKOVSLDWIHYSY-ACZMJKKPSA-N 0.000 description 3
- SUEIIIFUBHDCCS-PBCZWWQYSA-N Asn-His-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SUEIIIFUBHDCCS-PBCZWWQYSA-N 0.000 description 3
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 3
- ZYPWIUFLYMQZBS-SRVKXCTJSA-N Asn-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ZYPWIUFLYMQZBS-SRVKXCTJSA-N 0.000 description 3
- RTFWCVDISAMGEQ-SRVKXCTJSA-N Asn-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N RTFWCVDISAMGEQ-SRVKXCTJSA-N 0.000 description 3
- PPCORQFLAZWUNO-QWRGUYRKSA-N Asn-Phe-Gly Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(=O)N)N PPCORQFLAZWUNO-QWRGUYRKSA-N 0.000 description 3
- RVHGJNGNKGDCPX-KKUMJFAQSA-N Asn-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N RVHGJNGNKGDCPX-KKUMJFAQSA-N 0.000 description 3
- BKFXFUPYETWGGA-XVSYOHENSA-N Asn-Phe-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BKFXFUPYETWGGA-XVSYOHENSA-N 0.000 description 3
- XTMZYFMTYJNABC-ZLUOBGJFSA-N Asn-Ser-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N XTMZYFMTYJNABC-ZLUOBGJFSA-N 0.000 description 3
- NPZJLGMWMDNQDD-GHCJXIJMSA-N Asn-Ser-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NPZJLGMWMDNQDD-GHCJXIJMSA-N 0.000 description 3
- NCXTYSVDWLAQGZ-ZKWXMUAHSA-N Asn-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O NCXTYSVDWLAQGZ-ZKWXMUAHSA-N 0.000 description 3
- QUMKPKWYDVMGNT-NUMRIWBASA-N Asn-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QUMKPKWYDVMGNT-NUMRIWBASA-N 0.000 description 3
- PIABYSIYPGLLDQ-XVSYOHENSA-N Asn-Thr-Phe Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PIABYSIYPGLLDQ-XVSYOHENSA-N 0.000 description 3
- QNNBHTFDFFFHGC-KKUMJFAQSA-N Asn-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QNNBHTFDFFFHGC-KKUMJFAQSA-N 0.000 description 3
- HRGGPWBIMIQANI-GUBZILKMSA-N Asp-Gln-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HRGGPWBIMIQANI-GUBZILKMSA-N 0.000 description 3
- LTXGDRFJRZSZAV-CIUDSAMLSA-N Asp-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)N LTXGDRFJRZSZAV-CIUDSAMLSA-N 0.000 description 3
- PGUYEUCYVNZGGV-QWRGUYRKSA-N Asp-Gly-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PGUYEUCYVNZGGV-QWRGUYRKSA-N 0.000 description 3
- HOBNTSHITVVNBN-ZPFDUUQYSA-N Asp-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N HOBNTSHITVVNBN-ZPFDUUQYSA-N 0.000 description 3
- WZUZGDANRQPCDD-SRVKXCTJSA-N Asp-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N WZUZGDANRQPCDD-SRVKXCTJSA-N 0.000 description 3
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 3
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 3
- ZQFRDAZBTSFGGW-SRVKXCTJSA-N Asp-Ser-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZQFRDAZBTSFGGW-SRVKXCTJSA-N 0.000 description 3
- YIDFBWRHIYOYAA-LKXGYXEUSA-N Asp-Ser-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YIDFBWRHIYOYAA-LKXGYXEUSA-N 0.000 description 3
- CZIVKMOEXPILDK-SRVKXCTJSA-N Asp-Tyr-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(O)=O CZIVKMOEXPILDK-SRVKXCTJSA-N 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- XMTDCXXLDZKAGI-ACZMJKKPSA-N Cys-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N XMTDCXXLDZKAGI-ACZMJKKPSA-N 0.000 description 3
- NOCCABSVTRONIN-CIUDSAMLSA-N Cys-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CS)N NOCCABSVTRONIN-CIUDSAMLSA-N 0.000 description 3
- PRXCTTWKGJAPMT-ZLUOBGJFSA-N Cys-Ala-Ser Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O PRXCTTWKGJAPMT-ZLUOBGJFSA-N 0.000 description 3
- WDQXKVCQXRNOSI-GHCJXIJMSA-N Cys-Asp-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WDQXKVCQXRNOSI-GHCJXIJMSA-N 0.000 description 3
- VPQZSNQICFCCSO-BJDJZHNGSA-N Cys-Leu-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VPQZSNQICFCCSO-BJDJZHNGSA-N 0.000 description 3
- SNHRIJBANHPWMO-XGEHTFHBSA-N Cys-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)N)O SNHRIJBANHPWMO-XGEHTFHBSA-N 0.000 description 3
- BCWIFCLVCRAIQK-ZLUOBGJFSA-N Cys-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O BCWIFCLVCRAIQK-ZLUOBGJFSA-N 0.000 description 3
- JTEGHEWKBCTIAL-IXOXFDKPSA-N Cys-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CS)N)O JTEGHEWKBCTIAL-IXOXFDKPSA-N 0.000 description 3
- FCXJJTRGVAZDER-FXQIFTODSA-N Cys-Val-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O FCXJJTRGVAZDER-FXQIFTODSA-N 0.000 description 3
- KZZYVYWSXMFYEC-DCAQKATOSA-N Cys-Val-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KZZYVYWSXMFYEC-DCAQKATOSA-N 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KZEUVLLVULIPNX-GUBZILKMSA-N Gln-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N KZEUVLLVULIPNX-GUBZILKMSA-N 0.000 description 3
- LVNILKSSFHCSJZ-IHRRRGAJSA-N Gln-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LVNILKSSFHCSJZ-IHRRRGAJSA-N 0.000 description 3
- MAGNEQBFSBREJL-DCAQKATOSA-N Gln-Glu-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N MAGNEQBFSBREJL-DCAQKATOSA-N 0.000 description 3
- HDUDGCZEOZEFOA-KBIXCLLPSA-N Gln-Ile-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HDUDGCZEOZEFOA-KBIXCLLPSA-N 0.000 description 3
- RGAOLBZBLOJUTP-GRLWGSQLSA-N Gln-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H](CCC(=O)N)N RGAOLBZBLOJUTP-GRLWGSQLSA-N 0.000 description 3
- JKGHMESJHRTHIC-SIUGBPQLSA-N Gln-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JKGHMESJHRTHIC-SIUGBPQLSA-N 0.000 description 3
- PSERKXGRRADTKA-MNXVOIDGSA-N Gln-Leu-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PSERKXGRRADTKA-MNXVOIDGSA-N 0.000 description 3
- UESYBOXFJWJVSB-AVGNSLFASA-N Gln-Phe-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O UESYBOXFJWJVSB-AVGNSLFASA-N 0.000 description 3
- YRHZWVKUFWCEPW-GLLZPBPUSA-N Gln-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O YRHZWVKUFWCEPW-GLLZPBPUSA-N 0.000 description 3
- ZZLDMBMFKZFQMU-NRPADANISA-N Gln-Val-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O ZZLDMBMFKZFQMU-NRPADANISA-N 0.000 description 3
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 3
- CKRUHITYRFNUKW-WDSKDSINSA-N Glu-Asn-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O CKRUHITYRFNUKW-WDSKDSINSA-N 0.000 description 3
- JVSBYEDSSRZQGV-GUBZILKMSA-N Glu-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O JVSBYEDSSRZQGV-GUBZILKMSA-N 0.000 description 3
- KVBPDJIFRQUQFY-ACZMJKKPSA-N Glu-Cys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O KVBPDJIFRQUQFY-ACZMJKKPSA-N 0.000 description 3
- HILMIYALTUQTRC-XVKPBYJWSA-N Glu-Gly-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HILMIYALTUQTRC-XVKPBYJWSA-N 0.000 description 3
- LGYCLOCORAEQSZ-PEFMBERDSA-N Glu-Ile-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O LGYCLOCORAEQSZ-PEFMBERDSA-N 0.000 description 3
- KXTAGESXNQEZKB-DZKIICNBSA-N Glu-Phe-Val Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 KXTAGESXNQEZKB-DZKIICNBSA-N 0.000 description 3
- RFTVTKBHDXCEEX-WDSKDSINSA-N Glu-Ser-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RFTVTKBHDXCEEX-WDSKDSINSA-N 0.000 description 3
- HBMRTXJZQDVRFT-DZKIICNBSA-N Glu-Tyr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O HBMRTXJZQDVRFT-DZKIICNBSA-N 0.000 description 3
- KIEICAOUSNYOLM-NRPADANISA-N Glu-Val-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O KIEICAOUSNYOLM-NRPADANISA-N 0.000 description 3
- MLILEEIVMRUYBX-NHCYSSNCSA-N Glu-Val-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MLILEEIVMRUYBX-NHCYSSNCSA-N 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
- UGVQELHRNUDMAA-BYPYZUCNSA-N Gly-Ala-Gly Chemical compound [NH3+]CC(=O)N[C@@H](C)C(=O)NCC([O-])=O UGVQELHRNUDMAA-BYPYZUCNSA-N 0.000 description 3
- CLODWIOAKCSBAN-BQBZGAKWSA-N Gly-Arg-Asp Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O CLODWIOAKCSBAN-BQBZGAKWSA-N 0.000 description 3
- LURCIJSJAKFCRO-QWRGUYRKSA-N Gly-Asn-Tyr Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LURCIJSJAKFCRO-QWRGUYRKSA-N 0.000 description 3
- SUDUYJOBLHQAMI-WHFBIAKZSA-N Gly-Asp-Cys Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(O)=O SUDUYJOBLHQAMI-WHFBIAKZSA-N 0.000 description 3
- PEZZSFLFXXFUQD-XPUUQOCRSA-N Gly-Cys-Val Chemical compound [H]NCC(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O PEZZSFLFXXFUQD-XPUUQOCRSA-N 0.000 description 3
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 description 3
- JSNNHGHYGYMVCK-XVKPBYJWSA-N Gly-Glu-Val Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JSNNHGHYGYMVCK-XVKPBYJWSA-N 0.000 description 3
- HMHRTKOWRUPPNU-RCOVLWMOSA-N Gly-Ile-Gly Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O HMHRTKOWRUPPNU-RCOVLWMOSA-N 0.000 description 3
- COVXELOAORHTND-LSJOCFKGSA-N Gly-Ile-Val Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O COVXELOAORHTND-LSJOCFKGSA-N 0.000 description 3
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 3
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 3
- LBDXVCBAJJNJNN-WHFBIAKZSA-N Gly-Ser-Cys Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O LBDXVCBAJJNJNN-WHFBIAKZSA-N 0.000 description 3
- POJJAZJHBGXEGM-YUMQZZPRSA-N Gly-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN POJJAZJHBGXEGM-YUMQZZPRSA-N 0.000 description 3
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 3
- YDIDLLVFCYSXNY-RCOVLWMOSA-N Gly-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)CN YDIDLLVFCYSXNY-RCOVLWMOSA-N 0.000 description 3
- RYAOJUMWLWUGNW-QMMMGPOBSA-N Gly-Val-Gly Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O RYAOJUMWLWUGNW-QMMMGPOBSA-N 0.000 description 3
- BAYQNCWLXIDLHX-ONGXEEELSA-N Gly-Val-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN BAYQNCWLXIDLHX-ONGXEEELSA-N 0.000 description 3
- KSOBNUBCYHGUKH-UWVGGRQHSA-N Gly-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN KSOBNUBCYHGUKH-UWVGGRQHSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101710114810 Glycoprotein Proteins 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 3
- LSQHWKPPOFDHHZ-YUMQZZPRSA-N His-Asp-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N LSQHWKPPOFDHHZ-YUMQZZPRSA-N 0.000 description 3
- UPJODPVSKKWGDQ-KLHWPWHYSA-N His-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O UPJODPVSKKWGDQ-KLHWPWHYSA-N 0.000 description 3
- KECFCPNPPYCGBL-PMVMPFDFSA-N His-Trp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CC4=CN=CN4)N KECFCPNPPYCGBL-PMVMPFDFSA-N 0.000 description 3
- GYXDQXPCPASCNR-NHCYSSNCSA-N His-Val-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N GYXDQXPCPASCNR-NHCYSSNCSA-N 0.000 description 3
- NKVZTQVGUNLLQW-JBDRJPRFSA-N Ile-Ala-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)O)N NKVZTQVGUNLLQW-JBDRJPRFSA-N 0.000 description 3
- VSZALHITQINTGC-GHCJXIJMSA-N Ile-Ala-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)O)N VSZALHITQINTGC-GHCJXIJMSA-N 0.000 description 3
- YKRYHWJRQUSTKG-KBIXCLLPSA-N Ile-Ala-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKRYHWJRQUSTKG-KBIXCLLPSA-N 0.000 description 3
- AQCUAZTZSPQJFF-ZKWXMUAHSA-N Ile-Ala-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O AQCUAZTZSPQJFF-ZKWXMUAHSA-N 0.000 description 3
- YPQDTQJBOFOTJQ-SXTJYALSSA-N Ile-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N YPQDTQJBOFOTJQ-SXTJYALSSA-N 0.000 description 3
- PFTFEWHJSAXGED-ZKWXMUAHSA-N Ile-Cys-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N PFTFEWHJSAXGED-ZKWXMUAHSA-N 0.000 description 3
- GECLQMBTZCPAFY-PEFMBERDSA-N Ile-Gln-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N GECLQMBTZCPAFY-PEFMBERDSA-N 0.000 description 3
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-N 0.000 description 3
- PDTMWFVVNZYWTR-NHCYSSNCSA-N Ile-Gly-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O PDTMWFVVNZYWTR-NHCYSSNCSA-N 0.000 description 3
- PMMMQRVUMVURGJ-XUXIUFHCSA-N Ile-Leu-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O PMMMQRVUMVURGJ-XUXIUFHCSA-N 0.000 description 3
- RMNMUUCYTMLWNA-ZPFDUUQYSA-N Ile-Lys-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RMNMUUCYTMLWNA-ZPFDUUQYSA-N 0.000 description 3
- CIJLNXXMDUOFPH-HJWJTTGWSA-N Ile-Pro-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CIJLNXXMDUOFPH-HJWJTTGWSA-N 0.000 description 3
- JODPUDMBQBIWCK-GHCJXIJMSA-N Ile-Ser-Asn Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O JODPUDMBQBIWCK-GHCJXIJMSA-N 0.000 description 3
- SAEWJTCJQVZQNZ-IUKAMOBKSA-N Ile-Thr-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N SAEWJTCJQVZQNZ-IUKAMOBKSA-N 0.000 description 3
- ANTFEOSJMAUGIB-KNZXXDILSA-N Ile-Thr-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N ANTFEOSJMAUGIB-KNZXXDILSA-N 0.000 description 3
- IPFKIGNDTUOFAF-CYDGBPFRSA-N Ile-Val-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IPFKIGNDTUOFAF-CYDGBPFRSA-N 0.000 description 3
- ZSESFIFAYQEKRD-CYDGBPFRSA-N Ile-Val-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(=O)O)N ZSESFIFAYQEKRD-CYDGBPFRSA-N 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 3
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 3
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- ZRLUISBDKUWAIZ-CIUDSAMLSA-N Leu-Ala-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O ZRLUISBDKUWAIZ-CIUDSAMLSA-N 0.000 description 3
- FIJMQLGQLBLBOL-HJGDQZAQSA-N Leu-Asn-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FIJMQLGQLBLBOL-HJGDQZAQSA-N 0.000 description 3
- KTFHTMHHKXUYPW-ZPFDUUQYSA-N Leu-Asp-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KTFHTMHHKXUYPW-ZPFDUUQYSA-N 0.000 description 3
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 3
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 3
- QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 description 3
- YORLGJINWYYIMX-KKUMJFAQSA-N Leu-Cys-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YORLGJINWYYIMX-KKUMJFAQSA-N 0.000 description 3
- HUEBCHPSXSQUGN-GARJFASQSA-N Leu-Cys-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N HUEBCHPSXSQUGN-GARJFASQSA-N 0.000 description 3
- ZTLGVASZOIKNIX-DCAQKATOSA-N Leu-Gln-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N ZTLGVASZOIKNIX-DCAQKATOSA-N 0.000 description 3
- GPICTNQYKHHHTH-GUBZILKMSA-N Leu-Gln-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GPICTNQYKHHHTH-GUBZILKMSA-N 0.000 description 3
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 3
- HPBCTWSUJOGJSH-MNXVOIDGSA-N Leu-Glu-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HPBCTWSUJOGJSH-MNXVOIDGSA-N 0.000 description 3
- OGUUKPXUTHOIAV-SDDRHHMPSA-N Leu-Glu-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGUUKPXUTHOIAV-SDDRHHMPSA-N 0.000 description 3
- LAPSXOAUPNOINL-YUMQZZPRSA-N Leu-Gly-Asp Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O LAPSXOAUPNOINL-YUMQZZPRSA-N 0.000 description 3
- KEVYYIMVELOXCT-KBPBESRZSA-N Leu-Gly-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KEVYYIMVELOXCT-KBPBESRZSA-N 0.000 description 3
- PBGDOSARRIJMEV-DLOVCJGASA-N Leu-His-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O PBGDOSARRIJMEV-DLOVCJGASA-N 0.000 description 3
- KOSWSHVQIVTVQF-ZPFDUUQYSA-N Leu-Ile-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KOSWSHVQIVTVQF-ZPFDUUQYSA-N 0.000 description 3
- VCHVSKNMTXWIIP-SRVKXCTJSA-N Leu-Lys-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O VCHVSKNMTXWIIP-SRVKXCTJSA-N 0.000 description 3
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-N 0.000 description 3
- VDIARPPNADFEAV-WEDXCCLWSA-N Leu-Thr-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O VDIARPPNADFEAV-WEDXCCLWSA-N 0.000 description 3
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 3
- BTSXLXFPMZXVPR-DLOVCJGASA-N Lys-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCCN)N BTSXLXFPMZXVPR-DLOVCJGASA-N 0.000 description 3
- NTSPQIONFJUMJV-AVGNSLFASA-N Lys-Arg-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O NTSPQIONFJUMJV-AVGNSLFASA-N 0.000 description 3
- DEFGUIIUYAUEDU-ZPFDUUQYSA-N Lys-Asn-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DEFGUIIUYAUEDU-ZPFDUUQYSA-N 0.000 description 3
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 3
- XFBBBRDEQIPGNR-KATARQTJSA-N Lys-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N)O XFBBBRDEQIPGNR-KATARQTJSA-N 0.000 description 3
- OPTCSTACHGNULU-DCAQKATOSA-N Lys-Cys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN OPTCSTACHGNULU-DCAQKATOSA-N 0.000 description 3
- VSRXPEHZMHSFKU-IUCAKERBSA-N Lys-Gln-Gly Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O VSRXPEHZMHSFKU-IUCAKERBSA-N 0.000 description 3
- IRRZDAIFYHNIIN-JYJNAYRXSA-N Lys-Gln-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IRRZDAIFYHNIIN-JYJNAYRXSA-N 0.000 description 3
- PBIPLDMFHAICIP-DCAQKATOSA-N Lys-Glu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PBIPLDMFHAICIP-DCAQKATOSA-N 0.000 description 3
- DKTNGXVSCZULPO-YUMQZZPRSA-N Lys-Gly-Cys Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CS)C(O)=O DKTNGXVSCZULPO-YUMQZZPRSA-N 0.000 description 3
- DTUZCYRNEJDKSR-NHCYSSNCSA-N Lys-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN DTUZCYRNEJDKSR-NHCYSSNCSA-N 0.000 description 3
- HAUUXTXKJNVIFY-ONGXEEELSA-N Lys-Gly-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAUUXTXKJNVIFY-ONGXEEELSA-N 0.000 description 3
- ONPDTSFZAIWMDI-AVGNSLFASA-N Lys-Leu-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ONPDTSFZAIWMDI-AVGNSLFASA-N 0.000 description 3
- QKXZCUCBFPEXNK-KKUMJFAQSA-N Lys-Leu-His Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 QKXZCUCBFPEXNK-KKUMJFAQSA-N 0.000 description 3
- ODTZHNZPINULEU-KKUMJFAQSA-N Lys-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N ODTZHNZPINULEU-KKUMJFAQSA-N 0.000 description 3
- ZVXSESPJMKNIQA-YXMSTPNBSA-N Lys-Thr-Pro-Pro Chemical compound NCCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 ZVXSESPJMKNIQA-YXMSTPNBSA-N 0.000 description 3
- PELXPRPDQRFBGQ-KKUMJFAQSA-N Lys-Tyr-Asn Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N)O PELXPRPDQRFBGQ-KKUMJFAQSA-N 0.000 description 3
- VKCPHIOZDWUFSW-ONGXEEELSA-N Lys-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN VKCPHIOZDWUFSW-ONGXEEELSA-N 0.000 description 3
- RIPJMCFGQHGHNP-RHYQMDGZSA-N Lys-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)N)O RIPJMCFGQHGHNP-RHYQMDGZSA-N 0.000 description 3
- BVXXDMUMHMXFER-BPNCWPANSA-N Met-Ala-Tyr Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BVXXDMUMHMXFER-BPNCWPANSA-N 0.000 description 3
- RBGLBUDVQVPTEG-DCAQKATOSA-N Met-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCSC)N RBGLBUDVQVPTEG-DCAQKATOSA-N 0.000 description 3
- RMLLCGYYVZKKRT-CIUDSAMLSA-N Met-Ser-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O RMLLCGYYVZKKRT-CIUDSAMLSA-N 0.000 description 3
- HLZORBMOISUNIV-DCAQKATOSA-N Met-Ser-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C HLZORBMOISUNIV-DCAQKATOSA-N 0.000 description 3
- FIZZULTXMVEIAA-IHRRRGAJSA-N Met-Ser-Phe Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FIZZULTXMVEIAA-IHRRRGAJSA-N 0.000 description 3
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 3
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
- 108010087066 N2-tryptophyllysine Proteins 0.000 description 3
- UUWCIPUVJJIEEP-SRVKXCTJSA-N Phe-Asn-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N UUWCIPUVJJIEEP-SRVKXCTJSA-N 0.000 description 3
- NKLDZIPTGKBDBB-HTUGSXCWSA-N Phe-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N)O NKLDZIPTGKBDBB-HTUGSXCWSA-N 0.000 description 3
- HOYQLNNGMHXZDW-KKUMJFAQSA-N Phe-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HOYQLNNGMHXZDW-KKUMJFAQSA-N 0.000 description 3
- KJJROSNFBRWPHS-JYJNAYRXSA-N Phe-Glu-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O KJJROSNFBRWPHS-JYJNAYRXSA-N 0.000 description 3
- METZZBCMDXHFMK-BZSNNMDCSA-N Phe-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N METZZBCMDXHFMK-BZSNNMDCSA-N 0.000 description 3
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 3
- KPEIBEPEUAZWNS-ULQDDVLXSA-N Phe-Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 KPEIBEPEUAZWNS-ULQDDVLXSA-N 0.000 description 3
- CJAHQEZWDZNSJO-KKUMJFAQSA-N Phe-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 CJAHQEZWDZNSJO-KKUMJFAQSA-N 0.000 description 3
- ZUQACJLOHYRVPJ-DKIMLUQUSA-N Phe-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 ZUQACJLOHYRVPJ-DKIMLUQUSA-N 0.000 description 3
- AFNJAQVMTIQTCB-DLOVCJGASA-N Phe-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 AFNJAQVMTIQTCB-DLOVCJGASA-N 0.000 description 3
- IAOZOFPONWDXNT-IXOXFDKPSA-N Phe-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IAOZOFPONWDXNT-IXOXFDKPSA-N 0.000 description 3
- IEIFEYBAYFSRBQ-IHRRRGAJSA-N Phe-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IEIFEYBAYFSRBQ-IHRRRGAJSA-N 0.000 description 3
- 108091036407 Polyadenylation Proteins 0.000 description 3
- HFZNNDWPHBRNPV-KZVJFYERSA-N Pro-Ala-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HFZNNDWPHBRNPV-KZVJFYERSA-N 0.000 description 3
- ZSKJPKFTPQCPIH-RCWTZXSCSA-N Pro-Arg-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZSKJPKFTPQCPIH-RCWTZXSCSA-N 0.000 description 3
- LUGOKRWYNMDGTD-FXQIFTODSA-N Pro-Cys-Asn Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O LUGOKRWYNMDGTD-FXQIFTODSA-N 0.000 description 3
- ZPPVJIJMIKTERM-YUMQZZPRSA-N Pro-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]1CCCN1 ZPPVJIJMIKTERM-YUMQZZPRSA-N 0.000 description 3
- DIFXZGPHVCIVSQ-CIUDSAMLSA-N Pro-Gln-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O DIFXZGPHVCIVSQ-CIUDSAMLSA-N 0.000 description 3
- XZONQWUEBAFQPO-HJGDQZAQSA-N Pro-Gln-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XZONQWUEBAFQPO-HJGDQZAQSA-N 0.000 description 3
- NXEYSLRNNPWCRN-SRVKXCTJSA-N Pro-Glu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NXEYSLRNNPWCRN-SRVKXCTJSA-N 0.000 description 3
- JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 description 3
- GURGCNUWVSDYTP-SRVKXCTJSA-N Pro-Leu-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O GURGCNUWVSDYTP-SRVKXCTJSA-N 0.000 description 3
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 3
- DWGFLKQSGRUQTI-IHRRRGAJSA-N Pro-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1 DWGFLKQSGRUQTI-IHRRRGAJSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 3
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 3
- OOKCGAYXSNJBGQ-ZLUOBGJFSA-N Ser-Asn-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O OOKCGAYXSNJBGQ-ZLUOBGJFSA-N 0.000 description 3
- KAAPNMOKUUPKOE-SRVKXCTJSA-N Ser-Asn-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KAAPNMOKUUPKOE-SRVKXCTJSA-N 0.000 description 3
- DSSOYPJWSWFOLK-CIUDSAMLSA-N Ser-Cys-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O DSSOYPJWSWFOLK-CIUDSAMLSA-N 0.000 description 3
- YPUSXTWURJANKF-KBIXCLLPSA-N Ser-Gln-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O YPUSXTWURJANKF-KBIXCLLPSA-N 0.000 description 3
- BQWCDDAISCPDQV-XHNCKOQMSA-N Ser-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N)C(=O)O BQWCDDAISCPDQV-XHNCKOQMSA-N 0.000 description 3
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 3
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 3
- HBTCFCHYALPXME-HTFCKZLJSA-N Ser-Ile-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HBTCFCHYALPXME-HTFCKZLJSA-N 0.000 description 3
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 3
- HJAXVYLCKDPPDF-SRVKXCTJSA-N Ser-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N HJAXVYLCKDPPDF-SRVKXCTJSA-N 0.000 description 3
- XKFJENWJGHMDLI-QWRGUYRKSA-N Ser-Phe-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O XKFJENWJGHMDLI-QWRGUYRKSA-N 0.000 description 3
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 3
- PJIQEIFXZPCWOJ-FXQIFTODSA-N Ser-Pro-Asp Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O PJIQEIFXZPCWOJ-FXQIFTODSA-N 0.000 description 3
- FLONGDPORFIVQW-XGEHTFHBSA-N Ser-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FLONGDPORFIVQW-XGEHTFHBSA-N 0.000 description 3
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 3
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 3
- QYBRQMLZDDJBSW-AVGNSLFASA-N Ser-Tyr-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O QYBRQMLZDDJBSW-AVGNSLFASA-N 0.000 description 3
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 3
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 3
- 101710167605 Spike glycoprotein Proteins 0.000 description 3
- TYVAWPFQYFPSBR-BFHQHQDPSA-N Thr-Ala-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(O)=O TYVAWPFQYFPSBR-BFHQHQDPSA-N 0.000 description 3
- LVHHEVGYAZGXDE-KDXUFGMBSA-N Thr-Ala-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(=O)O)N)O LVHHEVGYAZGXDE-KDXUFGMBSA-N 0.000 description 3
- SKHPKKYKDYULDH-HJGDQZAQSA-N Thr-Asn-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O SKHPKKYKDYULDH-HJGDQZAQSA-N 0.000 description 3
- JBHMLZSKIXMVFS-XVSYOHENSA-N Thr-Asn-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JBHMLZSKIXMVFS-XVSYOHENSA-N 0.000 description 3
- PZVGOVRNGKEFCB-KKHAAJSZSA-N Thr-Asn-Val Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N)O PZVGOVRNGKEFCB-KKHAAJSZSA-N 0.000 description 3
- RKDFEMGVMMYYNG-WDCWCFNPSA-N Thr-Gln-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O RKDFEMGVMMYYNG-WDCWCFNPSA-N 0.000 description 3
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 3
- KBBRNEDOYWMIJP-KYNKHSRBSA-N Thr-Gly-Thr Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KBBRNEDOYWMIJP-KYNKHSRBSA-N 0.000 description 3
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 3
- JWQNAFHCXKVZKZ-UVOCVTCTSA-N Thr-Lys-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JWQNAFHCXKVZKZ-UVOCVTCTSA-N 0.000 description 3
- FDQXPJCLVPFKJW-KJEVXHAQSA-N Thr-Met-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N)O FDQXPJCLVPFKJW-KJEVXHAQSA-N 0.000 description 3
- DNCUODYZAMHLCV-XGEHTFHBSA-N Thr-Pro-Cys Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)O)N)O DNCUODYZAMHLCV-XGEHTFHBSA-N 0.000 description 3
- GVMXJJAJLIEASL-ZJDVBMNYSA-N Thr-Pro-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVMXJJAJLIEASL-ZJDVBMNYSA-N 0.000 description 3
- STUAPCLEDMKXKL-LKXGYXEUSA-N Thr-Ser-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O STUAPCLEDMKXKL-LKXGYXEUSA-N 0.000 description 3
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 3
- YRJOLUDFVAUXLI-GSSVUCPTSA-N Thr-Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O YRJOLUDFVAUXLI-GSSVUCPTSA-N 0.000 description 3
- VBMOVTMNHWPZJR-SUSMZKCASA-N Thr-Thr-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VBMOVTMNHWPZJR-SUSMZKCASA-N 0.000 description 3
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 3
- KPMIQCXJDVKWKO-IFFSRLJSSA-N Thr-Val-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPMIQCXJDVKWKO-IFFSRLJSSA-N 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- ICNFHVUVCNWUAB-SZMVWBNQSA-N Trp-Arg-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N ICNFHVUVCNWUAB-SZMVWBNQSA-N 0.000 description 3
- JGLXHHQUSIULAK-OYDLWJJNSA-N Trp-Pro-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC=3C4=CC=CC=C4NC=3)N)C(O)=O)=CNC2=C1 JGLXHHQUSIULAK-OYDLWJJNSA-N 0.000 description 3
- YXSSXUIBUJGHJY-SFJXLCSZSA-N Trp-Thr-Phe Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)[C@H](O)C)C(O)=O)C1=CC=CC=C1 YXSSXUIBUJGHJY-SFJXLCSZSA-N 0.000 description 3
- BURPTJBFWIOHEY-UWJYBYFXSA-N Tyr-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BURPTJBFWIOHEY-UWJYBYFXSA-N 0.000 description 3
- FBVGQXJIXFZKSQ-GMVOTWDCSA-N Tyr-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N FBVGQXJIXFZKSQ-GMVOTWDCSA-N 0.000 description 3
- DYEGCOJHFNJBKB-UFYCRDLUSA-N Tyr-Arg-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 DYEGCOJHFNJBKB-UFYCRDLUSA-N 0.000 description 3
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 3
- QHEGAOPHISYNDF-XDTLVQLUSA-N Tyr-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N QHEGAOPHISYNDF-XDTLVQLUSA-N 0.000 description 3
- CKHQKYHIZCRTAP-SOUVJXGZSA-N Tyr-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O CKHQKYHIZCRTAP-SOUVJXGZSA-N 0.000 description 3
- MPKPIWFFDWVJGC-IRIUXVKKSA-N Tyr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O MPKPIWFFDWVJGC-IRIUXVKKSA-N 0.000 description 3
- WAPFQMXRSDEGOE-IHRRRGAJSA-N Tyr-Glu-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O WAPFQMXRSDEGOE-IHRRRGAJSA-N 0.000 description 3
- LHTGRUZSZOIAKM-SOUVJXGZSA-N Tyr-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O LHTGRUZSZOIAKM-SOUVJXGZSA-N 0.000 description 3
- NOOMDULIORCDNF-IRXDYDNUSA-N Tyr-Gly-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NOOMDULIORCDNF-IRXDYDNUSA-N 0.000 description 3
- CTDPLKMBVALCGN-JSGCOSHPSA-N Tyr-Gly-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O CTDPLKMBVALCGN-JSGCOSHPSA-N 0.000 description 3
- FBHBVXUBTYVCRU-BZSNNMDCSA-N Tyr-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CN=CN1 FBHBVXUBTYVCRU-BZSNNMDCSA-N 0.000 description 3
- WSFXJLFSJSXGMQ-MGHWNKPDSA-N Tyr-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N WSFXJLFSJSXGMQ-MGHWNKPDSA-N 0.000 description 3
- LQGDFDYGDQEMGA-PXDAIIFMSA-N Tyr-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N LQGDFDYGDQEMGA-PXDAIIFMSA-N 0.000 description 3
- PSALWJCUIAQKFW-ACRUOGEOSA-N Tyr-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N PSALWJCUIAQKFW-ACRUOGEOSA-N 0.000 description 3
- WURLIFOWSMBUAR-SLFFLAALSA-N Tyr-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O WURLIFOWSMBUAR-SLFFLAALSA-N 0.000 description 3
- SOAUMCDLIUGXJJ-SRVKXCTJSA-N Tyr-Ser-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O SOAUMCDLIUGXJJ-SRVKXCTJSA-N 0.000 description 3
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 3
- LUMQYLVYUIRHHU-YJRXYDGGSA-N Tyr-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LUMQYLVYUIRHHU-YJRXYDGGSA-N 0.000 description 3
- WQOHKVRQDLNDIL-YJRXYDGGSA-N Tyr-Thr-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O WQOHKVRQDLNDIL-YJRXYDGGSA-N 0.000 description 3
- FPCIBLUVDNXPJO-XPUUQOCRSA-N Val-Cys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O FPCIBLUVDNXPJO-XPUUQOCRSA-N 0.000 description 3
- CPTQYHDSVGVGDZ-UKJIMTQDSA-N Val-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N CPTQYHDSVGVGDZ-UKJIMTQDSA-N 0.000 description 3
- VVZDBPBZHLQPPB-XVKPBYJWSA-N Val-Glu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VVZDBPBZHLQPPB-XVKPBYJWSA-N 0.000 description 3
- ZHQWPWQNVRCXAX-XQQFMLRXSA-N Val-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZHQWPWQNVRCXAX-XQQFMLRXSA-N 0.000 description 3
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 3
- XXWBHOWRARMUOC-NHCYSSNCSA-N Val-Lys-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)O)N XXWBHOWRARMUOC-NHCYSSNCSA-N 0.000 description 3
- XBJKAZATRJBDCU-GUBZILKMSA-N Val-Pro-Ala Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XBJKAZATRJBDCU-GUBZILKMSA-N 0.000 description 3
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 3
- DLLRRUDLMSJTMB-GUBZILKMSA-N Val-Ser-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)O)N DLLRRUDLMSJTMB-GUBZILKMSA-N 0.000 description 3
- NZYNRRGJJVSSTJ-GUBZILKMSA-N Val-Ser-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NZYNRRGJJVSSTJ-GUBZILKMSA-N 0.000 description 3
- WUFHZIRMAZZWRS-OSUNSFLBSA-N Val-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)N WUFHZIRMAZZWRS-OSUNSFLBSA-N 0.000 description 3
- YLBNZCJFSVJDRJ-KJEVXHAQSA-N Val-Thr-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O YLBNZCJFSVJDRJ-KJEVXHAQSA-N 0.000 description 3
- VTIAEOKFUJJBTC-YDHLFZDLSA-N Val-Tyr-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N VTIAEOKFUJJBTC-YDHLFZDLSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 108010013835 arginine glutamate Proteins 0.000 description 3
- 108010008355 arginyl-glutamine Proteins 0.000 description 3
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 108010016616 cysteinylglycine Proteins 0.000 description 3
- 210000000172 cytosol Anatomy 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 3
- 150000002019 disulfides Chemical class 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 3
- 108010078144 glutaminyl-glycine Proteins 0.000 description 3
- 229960003180 glutathione Drugs 0.000 description 3
- 108010089804 glycyl-threonine Proteins 0.000 description 3
- 108010015792 glycyllysine Proteins 0.000 description 3
- 108010081551 glycylphenylalanine Proteins 0.000 description 3
- 108010040030 histidinoalanine Proteins 0.000 description 3
- 108010036413 histidylglycine Proteins 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 3
- 108010034529 leucyl-lysine Proteins 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 108010018625 phenylalanylarginine Proteins 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108010079317 prolyl-tyrosine Proteins 0.000 description 3
- 108010015796 prolylisoleucine Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 108010044292 tryptophyltyrosine Proteins 0.000 description 3
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 3
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 2
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- HFPXZWPUVFVNLL-GUBZILKMSA-N Asn-Leu-Gln Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O HFPXZWPUVFVNLL-GUBZILKMSA-N 0.000 description 2
- XAJRHVUUVUPFQL-ACZMJKKPSA-N Asp-Glu-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O XAJRHVUUVUPFQL-ACZMJKKPSA-N 0.000 description 2
- MYLZFUMPZCPJCJ-NHCYSSNCSA-N Asp-Lys-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O MYLZFUMPZCPJCJ-NHCYSSNCSA-N 0.000 description 2
- BRRPVTUFESPTCP-ACZMJKKPSA-N Asp-Ser-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O BRRPVTUFESPTCP-ACZMJKKPSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- NLDWTJBJFVWBDQ-KKUMJFAQSA-N Cys-Lys-Phe Chemical compound NCCCC[C@H](NC(=O)[C@@H](N)CS)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 NLDWTJBJFVWBDQ-KKUMJFAQSA-N 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- RMOCFPBLHAOTDU-ACZMJKKPSA-N Gln-Asn-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O RMOCFPBLHAOTDU-ACZMJKKPSA-N 0.000 description 2
- UJMNFCAHLYKWOZ-DCAQKATOSA-N Glu-Lys-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O UJMNFCAHLYKWOZ-DCAQKATOSA-N 0.000 description 2
- KJBGAZSLZAQDPV-KKUMJFAQSA-N Glu-Phe-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N KJBGAZSLZAQDPV-KKUMJFAQSA-N 0.000 description 2
- VIIBEIQMLJEUJG-LAEOZQHASA-N Gly-Ile-Gln Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O VIIBEIQMLJEUJG-LAEOZQHASA-N 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 2
- 101100433975 Homo sapiens ACE2 gene Proteins 0.000 description 2
- AUIYHFRUOOKTGX-UKJIMTQDSA-N Ile-Val-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N AUIYHFRUOOKTGX-UKJIMTQDSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- QCHNRQQVLJYDSI-DLOVCJGASA-N Phe-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 QCHNRQQVLJYDSI-DLOVCJGASA-N 0.000 description 2
- MJAYDXWQQUOURZ-JYJNAYRXSA-N Phe-Lys-Gln Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O MJAYDXWQQUOURZ-JYJNAYRXSA-N 0.000 description 2
- RVEVENLSADZUMS-IHRRRGAJSA-N Phe-Pro-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O RVEVENLSADZUMS-IHRRRGAJSA-N 0.000 description 2
- HRIXMVRZRGFKNQ-HJGDQZAQSA-N Pro-Thr-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HRIXMVRZRGFKNQ-HJGDQZAQSA-N 0.000 description 2
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 2
- 229940022005 RNA vaccine Drugs 0.000 description 2
- 101000895926 Streptomyces plicatus Endo-beta-N-acetylglucosaminidase H Proteins 0.000 description 2
- 238000012288 TUNEL assay Methods 0.000 description 2
- RYHUIHUOYRNNIE-NRPADANISA-N Val-Ser-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N RYHUIHUOYRNNIE-NRPADANISA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000000246 agarose gel electrophoresis Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000003570 cell viability assay Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 108091036078 conserved sequence Proteins 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 235000021186 dishes Nutrition 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229960005030 other vaccine in atc Drugs 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000012846 protein folding Effects 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 238000009966 trimming Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000007502 viral entry Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- TTXMOJWKNRJWQJ-FXQIFTODSA-N Ala-Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CCCN=C(N)N TTXMOJWKNRJWQJ-FXQIFTODSA-N 0.000 description 1
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 1
- LNNSWWRRYJLGNI-NAKRPEOUSA-N Ala-Ile-Val Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O LNNSWWRRYJLGNI-NAKRPEOUSA-N 0.000 description 1
- QGNXYDHVERJIAY-ACZMJKKPSA-N Asn-Gln-Cys Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N QGNXYDHVERJIAY-ACZMJKKPSA-N 0.000 description 1
- BKOIIURTQAJHAT-GUBZILKMSA-N Asp-Pro-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 BKOIIURTQAJHAT-GUBZILKMSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 208000025721 COVID-19 Diseases 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 230000006782 ER associated degradation Effects 0.000 description 1
- 238000011510 Elispot assay Methods 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- LRQXRHGQEVWGPV-NHCYSSNCSA-N Gly-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN LRQXRHGQEVWGPV-NHCYSSNCSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 244000309467 Human Coronavirus Species 0.000 description 1
- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- AWMMBHDKERMOID-YTQUADARSA-N Lys-Trp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CCCCN)N)C(=O)O AWMMBHDKERMOID-YTQUADARSA-N 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- HLQWFLJOJRFXHO-CIUDSAMLSA-N Met-Glu-Ser Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O HLQWFLJOJRFXHO-CIUDSAMLSA-N 0.000 description 1
- IIHMNTBFPMRJCN-RCWTZXSCSA-N Met-Val-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IIHMNTBFPMRJCN-RCWTZXSCSA-N 0.000 description 1
- 101150030635 Mgat1 gene Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 229940026233 Pfizer-BioNTech COVID-19 vaccine Drugs 0.000 description 1
- VLZGUAUYZGQKPM-DRZSPHRISA-N Phe-Gln-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O VLZGUAUYZGQKPM-DRZSPHRISA-N 0.000 description 1
- VZFPYFRVHMSSNA-JURCDPSOSA-N Phe-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=CC=C1 VZFPYFRVHMSSNA-JURCDPSOSA-N 0.000 description 1
- CZQZSMJXFGGBHM-KKUMJFAQSA-N Phe-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O CZQZSMJXFGGBHM-KKUMJFAQSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Chemical class 0.000 description 1
- WHNJMTHJGCEKGA-ULQDDVLXSA-N Pro-Phe-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WHNJMTHJGCEKGA-ULQDDVLXSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101710146873 Receptor-binding protein Proteins 0.000 description 1
- 102000044437 S1 domains Human genes 0.000 description 1
- 108700036684 S1 domains Proteins 0.000 description 1
- 108091005634 SARS-CoV-2 receptor-binding domains Proteins 0.000 description 1
- 208000037847 SARS-CoV-2-infection Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- ZPZNQAZHMCLTOA-PXDAIIFMSA-N Trp-Tyr-Ile Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=C(O)C=C1 ZPZNQAZHMCLTOA-PXDAIIFMSA-N 0.000 description 1
- 101800001055 Truncated S protein Proteins 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 1
- 101710201961 Virion infectivity factor Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 150000001507 asparagine derivatives Chemical class 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- 108020005087 unfolded proteins Proteins 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 230000008478 viral entry into host cell Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/215—Coronaviridae, e.g. avian infectious bronchitis virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/08—RNA viruses
- C07K14/165—Coronaviridae, e.g. avian infectious bronchitis virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/20011—Coronaviridae
- C12N2770/20034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Dispersion Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本發明係關於在受體結合域(RBD)、次單元1 (S1)域、或次單元2 (S2)域、或其組合中具有醣位點缺失之冠狀病毒刺突蛋白的mRNA疫苗。該疫苗引發對冠狀病毒及其變種之廣泛保護性免疫反應。
Description
本發明大體上係關於治療及/或預防冠狀病毒感染之領域。特定言之,本發明係關於對抗廣譜冠狀病毒(CoV)變種的信使RNA (mRNA)疫苗。
在1796年,Edward Jenner創造了世界上第一個疫苗(牛痘)以抵禦天花,且成功拯救數百萬人,且此後接種疫苗已被認為係抵禦病原體之最佳方式。自2019年12月嚴重急性呼吸道症候群冠狀病毒-2 (SARS-CoV-2)之爆發(其引起冠狀病毒誘發之疾病2019 (COVID-19))以來,病毒擴散至全世界且在20個月內造成超過2億次感染及400萬例死亡。此大流行病已成為公眾健康之主要威脅。
大量工作已投入研發有效手段及疫苗以對抗此大流行病。病毒表面上之三聚刺突(S)蛋白為預防性疫苗及治療性抗體研發之關鍵免疫原及目標。截至2020年12月,美國FDA已授權Pfizer/BioNTech及Moderna之mRNA候選疫苗以及Regeneron之抗體用於緊急使用;但是,若干其他候選疫苗及人類抗體處於臨床試驗中,且其中有少數,包括Oxford/Astrazeneca及J&J疫苗接近獲得批准。在經研發以控制SARS-CoV-2及變種之擴散的各種疫苗中,由Moderna及BioNTech/Pfizer研發之mRNA疫苗由於速度及便利性而代表重大突破。此等疫苗用新mRNA技術及脂質奈米粒子(LNP)調配物來穩定化,以用於活體內遞送及轉譯成刺突(S)蛋白以誘發免疫反應(
Ewen Callaway . COVID vaccine excitement builds as Moderna reports third positive result . Nature . 587 ( 7834 ): 337 - 338 ( 2020 ); Polack P . 等人, Safety and Efficacy of the BNT162b2 mRNA Covid - 19 Vaccine . N Engl J Med . 383 ( 27 ): 2603 - 2615 ( 2020 ))。
然而,由於有許多變種在世界上廣泛傳播,且更具感染性之變種(諸如β、δ及o變種)對先前已接種疫苗及/或自早期形式之冠狀病毒感染恢復的人進行再感染之能力可能增強,因此由新出現之SARS-CoV-2變種引起的感染可能繼續出現或頻率可能增加。此RNA病毒之S蛋白經高度醣基化且頻繁突變,已向GISAID (www.gisaid.org)報告超過900萬個序列及其1,273個胺基酸之序列中超過1,000個突變位點,包括具有高度傳染性的δ及o變種,對廣泛有效抗體及疫苗研發構成重大挑戰。
因此,迫切需要更好的疫苗以及更好的產品及方法來預防及治療冠狀病毒感染。
本發明提供一種新穎冠狀病毒mRNA疫苗、其製備方法及其用途。新穎疫苗基於mRNA技術設計以移除冠狀病毒(例如SARS-CoV-2)刺突蛋白之聚醣屏蔽以更好地暴露刺突蛋白之保守區。冠狀病毒刺突蛋白之mRNA疫苗與未經修飾之mRNA相比,在受體結合域(RBD)或次單元2 (S2)域中缺失醣位點,以暴露高度保守之抗原決定基,且引發對抗α、β、γ、δ、o及不同變種之保護更廣泛的抗體及CD8 T細胞反應。本文提供之mRNA疫苗有效誘發對抗SARS-CoV-2及變種(例如α、β、γ、δ、o)之保護性免疫。當單獨或組合用作免疫原性組合物或疫苗時,本發明之mRNA疫苗可保護人免於感染及/或在感染時減輕症狀。
在一個態樣中,本發明提供至少一種免疫原性肽,其包含選自由以下組成之群的胺基酸序列:TESIVRFPNITNL (SEQ ID NO: 41)、NITNLCPFGEVFNATR (SEQ ID NO: 42)、LYNSASFSTFK (SEQ ID NO: 43)、LDSKVGGNYN (SEQ ID NO: 44)、KSNLKPFERDIST (SEQ ID NO: 45)、KPFERDISTEIYQAG (SEQ ID NO: 46)、GPKKSTNLVKNKC (SEQ ID NO: 47)、NCDVVIGIVNNTVY (SEQ ID NO: 48)、PELDSFKEELDKYFK[N]HTS (SEQ ID NO: 49)、VNIQKEIDRLNEVA (SEQ ID NO: 50)、NLNESLIDLQ (SEQ ID NO: 51)及LGKYEQYIKWP (SEQ ID NO: 52)或與SEQ ID NO: 41至52中之任一者具有至少約99%、98%、97%、96%、95%或90%一致性的胺基酸序列。
在一些實施例中,免疫原性肽包含選自由SEQ ID NO: 41至43及45至51組成之群的至少一個胺基酸序列。在一些實施例中,免疫原性肽包含SEQ ID NO: 41至52之至少一個、兩個、三個、四個、五個、六個、七個、八個、九個、十個、十一個或十二個胺基酸。在一些實施例中,免疫原性肽包含SEQ ID NO: 41至43及45至51之至少一個、兩個、三個、四個、五個、六個、七個、八個、九個、十個胺基酸。
在一個態樣中,本發明提供編碼經修飾刺突蛋白之經修飾核酸分子,該經修飾刺突蛋白包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處之胺基酸取代,其中X為除脯胺酸外之任何胺基酸殘基,且S/T表示絲胺酸或蘇胺酸殘基。
在一些實施例中,本文所描述之經修飾刺突蛋白包含在N鍵聯醣基化序列子(N-X-S/T)處天冬醯胺(N)經麩醯胺酸(Q)取代,以消除N鍵聯聚醣序列子。
在一些實施例中,本文所描述之經修飾刺突蛋白包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處的胺基酸取代,以消除N鍵聯聚醣序列子。
在一些實施例中,本文所描述之經修飾刺突蛋白包含一或多個在O鍵聯醣基化位點處的S/T之胺基酸取代,以消除O鍵聯醣基化位點。一個實例為S/T經丙胺酸(A)取代。
在一個實施例中,經修飾核酸分子為mRNA,或雙股或單股DNA。
在一個實施例中,經修飾刺突蛋白衍生自SARS-CoV-2刺突蛋白。本文所描述之SARS-CoV-2刺突蛋白包含SEQ ID NO: 2、16、18或20之胺基酸序列,或與SEQ ID NO: 2、16、18或20之胺基酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的胺基酸序列。
在一些實施例中,編碼SEQ ID NO: 2、16、18或20之胺基酸序列的核酸分子為分別包含SEQ ID NO: 1、15、17或19之核苷酸序列的mRNA,或分別包含與SEQ ID NO: 1、15、17或19之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列的mRNA。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 4、22、24或26之胺基酸序列,其中經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD)。編碼SEQ ID NO: 4、22、24或26之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 3、21、23或25之核苷酸序列,或分別包含與SEQ ID NO: 3、21、23或25之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 6、28、30或32之胺基酸序列,其中經修飾刺突蛋白包含缺少醣基化位點之S2次單元。編碼SEQ ID NO: 6、28、30或32之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 5、27、29或31之核苷酸序列,或分別包含與SEQ ID NO: 5、27、29或31之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 8或34之胺基酸序列,其中經修飾刺突蛋白包含由單個醣基化位點組成之S2次單元。在一些實施例中,該單個醣基化位點在位置N1194處。在一些實施例中,編碼SEQ ID NO: 8或34之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 7或33之核苷酸序列,或分別包含與SEQ ID NO: 7或33之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 10或36之胺基酸序列,其中經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD),及N801成為Q801之胺基酸取代。編碼SEQ ID NO: 10或36之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 9或35之核苷酸序列,或分別包含與SEQ ID NO: 9或35之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 12或38之胺基酸序列,其中經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD),及N1194成為Q1194之胺基酸取代。編碼SEQ ID NO: 12或38之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 11或37之核苷酸序列,或分別包含與SEQ ID NO: 11或37之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含SEQ ID NO: 14或40之胺基酸序列,其中經修飾刺突蛋白包含缺少醣基化位點之經修飾受體結合域(RBD),及N122成為Q122、N165成為Q165及N234成為Q234之胺基酸取代。編碼SEQ ID NO: 14或40之胺基酸序列的經修飾核酸分子分別包含SEQ ID NO: 13或39之核苷酸序列,或分別包含與SEQ ID NO: 13或39之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
在一些實施例中,本文所描述之經修飾刺突蛋白包含缺少醣基化位點之S1次單元。
在一些實施例中,本文所描述之經修飾刺突蛋白包含缺少醣基化位點之S1及S2次單元兩者。
本發明係關於冠狀病毒刺突蛋白之mRNA疫苗,其與未經修飾之mRNA相比,在受體結合域(RBD)或次單元2 (S2)域中缺失醣位點,以暴露高度保守之抗原決定基,且引發對抗α、β、γ、δ、o及不同變種之保護更廣泛的抗體及CD8 T細胞反應。
在一些實施例中,冠狀病毒疫苗包含在RBD或S2或其他域中具有醣位點之一或多個突變的冠狀病毒刺突蛋白mRNA,該等醣位點具有一或多個N成為Q或S/T成為A或其組合之置換。在另一實施例中,N-醣位點之突變為將推定序列子N-X-S/T變為Q-X-S/T,及/或將O-醣位點之S/T變為A。
在一些實施例中,具有N成為Q置換之醣位點的本文所描述之mRNA包括
S-(deg-RBD) (S蛋白,其中RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A)、S-(deg-S2) (S蛋白,其中S2中之所有9個醣位點由N突變為Q)、S-(deg-S2-1194) (S蛋白,其中除醣位點1194外,S2中之8個醣位點由N突變為Q)、S-(deg-RBD-801) (S蛋白,其中RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點801由N突變為Q)、S-(deg-RBD-1194) (S蛋白,其中RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點1194由N突變為Q),及S-(deg-RBD-122-165-234) (S蛋白,其中RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點122、165及234由N突變為Q)。
在一個實施例中,本發明之例示性冠狀病毒疫苗的免疫接種,如本文所描述,引起摺疊異常S蛋白在內質網中的積聚。在一個實施例中,本發明之例示性冠狀病毒疫苗的免疫接種,如本文所描述,引起BiP/GRP78、XBP1及p-eIF2α之上調以誘發細胞凋亡及CD8
+T細胞反應。在一個實施例中,本發明之例示性冠狀病毒疫苗的免疫接種,如本文所描述,可提高第I類主要組織相容複合體(MHC I)表現。
在一些實施例中,本文所描述之例示性CoV包括但不限於SARS-CoV、MERS-CoV及SARS-CoV-2。在一些實施例中,本文所描述之冠狀病毒(CoV)之實例包括但不限於α-SARS-CoV2、β-SARS-CoV2、γ-SARS-CoV2、δ-SARS-CoV2及ο-SARS-CoV2及其變種。
在一些實施例中,本發明提供包含啟動子、5'非轉譯區、3'非轉譯區、具有或不具有S-2P之表現質體及聚(A)尾信號序列的線性DNA,其中在表現質體上推定序列子N-X-S/T變為Q-X-S/T,且O-醣位點自S/T變為A。
在一些實施例中,S-2P表現質體包含SARS-CoV-2之S基因,其編碼具有K968及V969之脯胺酸取代的S的融合前狀態。
在一些實施例中,本發明提供一種藉由活體外轉譯自上述DNA製備之mRNA。
在另一態樣中,本發明提供一種載體,其包含上文所描述之經修飾核酸分子。
在另一態樣中,本發明提供一種宿主細胞,其包含上文所描述之經修飾核酸分子。
在另一態樣中,本發明提供上文所描述之經修飾刺突蛋白。
在另一態樣中,本發明提供一種用於遞送mRNA以在活體內產生蛋白質之方法,其包含:向個體投與包含本發明之編碼蛋白質的mRNA的組合物,其中mRNA囊封於脂質奈米粒子內,且其中投與組合物引起由mRNA編碼之蛋白質的表現。
在一些實施例中,如本文所描述之mRNA可單獨或與其他疫苗組合以用作疫苗。因此,本發明提供一種組合疫苗,其包含本發明之mRNA疫苗及一或多種額外疫苗。額外疫苗係選自一或多種COVID-19疫苗、流行性感冒(流感)疫苗、腺病毒疫苗、炭疽疫苗、霍亂疫苗、白喉疫苗、A或B型肝炎疫苗、HPV疫苗、麻疹疫苗、流行性腮腺炎疫苗、天花疫苗、輪狀病毒疫苗、肺結核疫苗、肺炎鏈球菌疫苗及b型流感嗜血桿菌(Haemophilus influenzae)疫苗及其任何組合。
在另一態樣中,本發明提供一種用作載劑之基於胍之奈米粒子,其用於將如請求項1至25中任一項之經修飾核酸分子遞送至個體。在一個實施例中,奈米粒子為脂質體或聚合物囊泡。
在另一態樣中,本發明提供一種mRNA奈米簇,其包含在脂質奈米粒子中調配之如本文所描述之mRNA疫苗。在一個實施例中,脂質奈米粒子為可生物降解的脂質奈米粒子。
在一些實施例中,如本文所描述之脂質奈米粒子為基於胍之聚合物。在一個實施例中,本發明提供一種mRNA奈米簇,其包含囊封有本文所描述之mRNA疫苗之脂質奈米粒子,其中脂質奈米粒子包含基於胍之聚合物單元,其中聚合物之基於胍及兩性離子之基團連接至聚合物之脂質尾,且其中基於胍之聚合物黏附於mRNA,由此在胍鎓基團與mRNA中之磷酸根之間形成鹽橋。基於胍之聚合物的實例包括但不限於如下文所示之P1、P2、P3、Pb及Pz。
,其中R為
。
在一些實施例中,基於胍之聚合物形成共聚物,諸如P1/P3共聚物、P2/P3共聚物、P1/Pb共聚物、P2/Pb共聚物、P1/Pz共聚物及P2/Pz共聚物。
在一些實施例中,本文所描述之mRNA奈米簇的奈米粒子/mRNA (N/P)比率為約1、約2、約3、約4、約5、約6、約7、約8、約9、約10、約15、約20、約30、約40、約50或約100。
在一些實施例中,本文所描述之mRNA奈米簇的奈米粒子/mRNA (N/P)比率為約10或約20。
在一些實施例中,本發明係關於一種奈米粒子/奈米簇組合物,其包含連接於本發明之冠狀病毒疫苗的奈米粒子。在一個實施例中,奈米粒子為脂質奈米粒子、聚合奈米粒子、無機奈米粒子(諸如金奈米粒子)、脂質體、免疫刺激複合物、類病毒粒子或自組裝蛋白。在另一實施例中,奈米粒子為脂質奈米粒子(LNP)。
在一些實施例中,本發明提供一種疫苗組合物,其包含如本文所描述之mRNA疫苗、mRNA奈米簇/奈米簇或奈米粒子組合物。
在一些實施例中,本發明係關於由本文所描述之疫苗引發之抗體及CD8+ T細胞,其具有對抗α、β、γ、δ,及ο變種之更廣泛保護。
在一些實施例中,本發明提供一種使個體免疫之方法,其包含投與本文所描述之疫苗組合物。本發明亦提供一種預防或治療冠狀病毒感染之方法,其包含向已感染冠狀病毒或處於感染冠狀病毒之風險下的個體投與有效量之如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物。在一個實施例中,如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物可用於增強適應性免疫反應之方法中。
在一些實施例中,如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物以初始劑量及兩次、三次或四次加強劑量投與。在一些實施例中,mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物以初始劑量投與,及在初始劑量之後約一個月、約兩個月、約三個月、約四個月、約五個月或約六個月,以至少一次加強劑量投與。在一些實施例中,所提供之組合物在初始劑量之後約六個月、約七個月、約八個月、約九個月、約十個月、約十一個月或約一年以第二次加強劑量投與。
在一些實施例中,mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物係以一或多次劑量投與。在一個實施例中,劑量可包括或不包括5 μg至50 μg mRNA。在一些實施例中,劑量為約5 μg、10 μg、15 μg、20 μg、25 μg、30 μg、35 μg、40 μg、45 μg或50 μg。
在一些實施例中,mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物係經由靜脈內途徑、肌肉內途徑、皮內途徑或皮下途徑投與或藉由輸注或鼻用噴霧投與。
在一些實施例中,本發明提供一種製備對抗SARS-CoV-2之廣泛保護性疫苗及抗體的方法。在一個實施例中,該方法包含使用天然或經醣改造之S蛋白的RNA或DNA來產生疫苗,而在抗原呈現細胞內表現之蛋白質,包括摺疊或未摺疊形式,經處理且呈現至T細胞。
此等及其他態樣由以下較佳實施例之描述結合以下圖式而將變得顯而易見,但可在不背離本發明之新穎構思的精神及範疇的情況下進行變化及修改。
序列表
本申請案含有序列表,其以ASCII格式以電子方式提交且以全文引用之方式併入本文中。
相關申請案之交叉參考
本申請案主張在2021年4月12日申請之USSN 63/173,752及在2021年12月1日申請之US 63/264,737的優先權,USSN 63/173,752及US 63/264,737之內容以全文引用之方式併入本文中。
本說明書中所使用之術語通常具有其在此項技術中、在本發明之上下文中及在使用各術語之特定上下文中之一般含義。在下文中或本說明書中其他地方論述了用於描述本發明之某些術語,以向從業者提供關於本發明之描述的額外指導。為方便起見,可能使用例如斜體字及/或引號突出顯示某些術語。突出顯示之使用對術語之範疇及含義無影響;在同一上下文中術語之範疇及含義相同,無論其是否突出顯示。應瞭解,同一事物可以超過一種方式傳達。因此,對於本文中論述之術語中之任一或多者,可使用替代語言及同義詞,無論術語在本文中是否詳細闡述或論述,均無任何特殊意義。提供了某些術語之同義詞。敍述一或多個同義詞並不排除使用其他同義詞。本說明書中任何地方之實例的使用僅為說明性的,其包括本文所論述之任何術語的實例,且決不限制本發明或任何例示術語之範疇及含義。同樣,本發明不限於在本說明書中給出之各種實施例。
必須指出,除非上下文另外明確指示,否則如本說明書及隨附申請專利範圍中所用,單數形式「一(a/an)」及「該」包括複數個指示物。
如本文所用,術語「刺突蛋白」及「刺突醣蛋白」及「冠狀病毒刺突蛋白」可互換使用。
如本文所用,術語「野生型(天然)冠狀病毒刺突蛋白」、「野生型(天然)冠狀病毒刺突醣蛋白」、「野生型(天然)刺突醣蛋白」及「野生型(天然)刺突蛋白」可互換使用。
如本文所用,術語「治療(treat/treatment/treating)」係指獲得有利或所需結果,例如臨床結果之方法。出於本發明之目的,有益或所要結果可包括抑制或遏制感染或疾病之起始或進展;緩解或減輕感染或疾病之症狀及發展;或其組合。
如本文所用,術語「預防(preventing/prevention)」可與「防治(prophylaxis)」互換使用,且可意謂完全預防感染或預防該感染之症狀發展;延緩感染或其症狀之發作;或減輕隨後發展之感染或其症狀之嚴重程度。
如本文所用,「有效量」係指足以誘發減輕至少一種病原體感染之症狀之免疫反應的免疫原之量。可例如藉由量測中和分泌及/或血清抗體之量,例如藉由溶菌斑中和、補體結合、酵素聯結免疫吸附(ELISA)或微量中和分析來測定有效劑量或有效量。
如本文所用,術語「疫苗」係指免疫原性劑(含或不含佐劑),諸如衍生自冠狀病毒的免疫原,其用於誘發對抗冠狀病毒的免疫反應,此提供保護性免疫(例如保護個體免於冠狀病毒感染及/或降低冠狀病毒感染所致的病狀的嚴重程度的免疫)。保護性免疫反應可包括抗體之形成及/或細胞介導之反應。視上下文而定,術語「疫苗」亦可指免疫原之懸浮液或溶液,其投與個體以產生保護性免疫。
如本文所用,術語「個體」包括人類及其他動物。通常,個體為人類。舉例而言,個體可為成人、青年、兒童(2歲至14歲)、嬰兒(出生至2歲)或新生兒(至多2個月)。在特定態樣中,個體至多4個月大或至多6個月大。在一些態樣中,成人為約65歲或更大或約60歲或更大的老年人。在一些態樣中,個體為孕婦或意欲懷孕之女性。在其他態樣中,個體不為人類;例如非人類靈長類動物;例如狒狒、黑猩猩、大猩猩或獼猴。在某些態樣中,個體可為寵物,諸如狗或貓。
如本文所用,術語「醫藥學上可接受」意謂經美國聯邦或州政府之監管機構批准,或在美國藥典、歐洲藥典或其他一般公認之藥典中列出,適用於哺乳動物,且更尤其適用於人類。此等組合物可用作在脊椎動物中誘發保護性免疫反應之疫苗及/或抗原組合物。
造成COVID-19的SARS-CoV-2之爆發已導致全球大流行。SARS-CoV-2感染之當前臨床管理包括預防、管制措施及支持性護理。為限制當前之大流行及未來可能之復發,更佳理解此病毒且研發用以對抗此類危險病原體之快速診斷方法、治療性治療及預防性疫苗很重要。大部分疫苗及抗體研發工作主要集中於經充分醣基化之SARS-CoV-2 S蛋白,其為病毒藉由結合至宿主細胞表面上之血管收縮素轉化酶2 (ACE2)受體而進入宿主細胞之重要介體。如同許多其他病毒融合蛋白,SARS-CoV-2 S蛋白利用聚醣包衣在融合前構形及融合後構形中遮蔽S蛋白主鏈,且避開宿主免疫反應。然而,轉譯後修飾如何在接種mRNA疫苗之後影響轉譯的免疫原仍然未知,且在轉譯後修飾事件中,醣基化在蛋白摺疊、結構及功能之調節中扮演重要角色。本發明旨在研發全長S蛋白及其次單元(包括S1或S2)及RBD域之經單GlcNAc裝飾及醣位點改造之變種(經由反向遺傳學移除非必需醣位點以用Gln置換Asn),作為免疫接種研究之候選疫苗,以產生抗原特異性中和抗體。
咸信開發新穎策略及廣泛保護性疫苗以對抗CoV感染可導向具有醫學意義之重要發現,但未以其他方式強調。在本發明中開發的原理及策略提供對抗不同CoV及其變種的通用冠狀病毒mRNA疫苗。
衍生自冠狀病毒刺突蛋白之免疫原性肽
迄今為止,已報導超過800萬個S蛋白之序列,在其1,273個胺基酸之序列中具有超過1,000個突變位點,包括高度傳染性D614G突變體,及來自英國及南非之突變體。此外,S蛋白上之所有醣位點均高度保守且S蛋白上之保守肽抗原決定基大部分由聚醣屏蔽。此在研發廣泛有效之抗體及疫苗以對抗即將出現之病毒株方面構成重大挑戰。本發明開發一種更有效的疫苗設計策略,其使用經改造醣基化之S蛋白作為免疫原,以更好地暴露用於疫苗設計之高度保守抗原決定基,以便誘發廣泛保護性免疫反應。
本發明發現移除病毒表面醣蛋白上之聚醣屏蔽以暴露更多保守抗原決定基為對抗SARS-CoV-2之疫苗設計的極有效方法。由於連接至Asn之單個GlcNAc殘基係醣蛋白摺疊及穩定化所需之
N-聚醣的最小組分,因此假定修剪
N-聚醣使單個GlcNAc留在SARS-CoV-2 S蛋白上將不影響其摺疊,但將促進蛋白主鏈最大暴露以誘發穩固且蛋白質特異性免疫反應,同時維持其結構完整性。
藉由移除SARS-CoV-2之刺突蛋白上的聚醣屏蔽,本發明提供一種免疫原性肽,其包含選自由以下組成之群的至少一個胺基酸序列:TESIVRFPNITNL (SEQ ID NO: 41)、NITNLCPFGEVFNATR (SEQ ID NO: 42)、LYNSASFSTFK (SEQ ID NO: 43)、LDSKVGGNYN (SEQ ID NO: 44)、KSNLKPFERDIST (SEQ ID NO: 45)、KPFERDISTEIYQAG (SEQ ID NO: 46)、GPKKSTNLVKNKC (SEQ ID NO: 47)、NCDVVIGIVNNTVY (SEQ ID NO: 48)、PELDSFKEELDKYFK[N]HTS (SEQ ID NO: 49)、VNIQKEIDRLNEVA (SEQ ID NO: 50)、NLNESLIDLQ (SEQ ID NO: 51)及LGKYEQYIKWP (SEQ ID NO: 52)或與SEQ ID NO: 41至52中之任一者具有至少約99%、98%、97%、96%、95%或90%一致性的胺基酸序列。
在一些實施例中,免疫原性肽包含選自由SEQ ID NO: 41至43及45至51組成之群的至少一個胺基酸序列。
SEQ ID NO: 41至52之胺基酸序列可單獨或組合用作能夠刺激對抗冠狀病毒之免疫反應的抗原。
習知方法,例如化學合成或重組技術,可用於製備如本文所描述之免疫原性肽。
免疫原性肽或能夠表現免疫原性肽之表現載體可與醫藥學上可接受之載劑混合以形成免疫原性組合物。組合物可投與有需要之個體以預防或治療冠狀病毒感染。
組合物可用醫藥學上可接受之載劑,諸如磷酸鹽緩衝鹽水、碳酸氫鹽溶液及/或佐劑調配。適合醫藥載劑及稀釋劑以及其使用需要之藥用輔料為此項技術中已知的。此組合物可製備成可注射劑、溶液、乳液或另一適合調配物。
佐劑之實例包括但不限於:明礬沈澱、弗氏完全佐劑(Freund's complete adjuvant)、弗氏不完全佐劑、CpG、QS21、單磷醯基-脂質A/海藻糖二黴菌酸酯佐劑、含有短小棒狀桿菌(Corynebacterium parvum)及tRNA之油包水乳液,及藉由模擬進化保守性分子之特定集合實現增加免疫反應之任務的其他物質,包括脂質體、脂多醣(LPS)、抗原之分子籠、細菌細胞壁之組分及內吞性核酸,諸如雙股RNA、單股DNA及未甲基化含CpG二核苷酸之DNA。其他實例包括霍亂毒素、大腸桿菌不耐熱腸毒素、脂質體、免疫刺激複合物(ISCOM)、免疫刺激序列寡去氧核苷酸及氫氧化鋁。組合物亦可包括促進活體內遞送之聚合物。
冠狀病毒
mRNA
疫苗
冠狀病毒(CoV)感染人類及動物且引起多種疾病,包括呼吸系統、腸道、腎臟及神經疾病。CoV使用其刺突醣蛋白(S) (一種中和抗體之主要目標)結合其受體且介導膜融合及病毒進入。冠狀病毒刺突蛋白在所有人類冠狀病毒(CoV)中高度保守且參與受體識別、病毒附著及進入宿主細胞中。類似地,SARS-CoV-2 S蛋白亦與CoV之S蛋白高度保守。SARS-CoV-2 S蛋白具有三個主要免疫原性域:N端域(NTD)、受體結合域(RBD)及次單元2域(S2)。先前研究已顯示,識別RBD之中和抗體(NAb)具有對抗SARS-CoV-2及其他冠狀病毒之高度保護性,及S蛋白經高度醣基化(每個單體24個醣位點)且頻繁突變,據GISAID報導有數百萬個序列。SARS-CoV-2 S蛋白之最保守區位於RBD及S2域中,其大部分由聚醣屏蔽(
Han - Yi Huang , 等人 Impact of glycosylation on a broad - spectrum vaccine against SARS - CoV - 2 . bioRxiv 預印本 . doi : www . biorxiv . org / content / 10 . 1101 / 2021 . 05 . 25 . 445523v2 . full),且抗體識別此等區域可提供對抗SARS-CoV-2之變種的廣泛保護(
Maximilian M Sauer . 等人 Structural basis for broad coronavirus neutralization . Nat Struct Mol Biol . 28 ( 6 ): 478 - 486 ( 2021 ) 1314; C.; Wang.等人A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies.
Nat Commun .12 (1):1715 (2021))。目標抗原或病原體上之醣基化會調節抗體誘發,但醣基化是否影響T細胞反應仍係未知的。實際上,很難或不可能自缺失某些醣基化位點之質體表現S蛋白(
Han - Yi Huang , 等人 Impact of glycosylation on a broad - spectrum vaccine against SARS - CoV - 2 . bioRxiv 預印本 . doi : www . biorxiv . org / content / 10 . 1101 / 2021 . 05 . 25 . 445523v2 . full)。
本發明意外地發現,使用mRNA技術移除聚醣屏蔽以更好地暴露保守區係廣譜疫苗設計之有效策略。在本發明中,具有特定醣位點突變之冠狀病毒刺突蛋白(諸如SARS-CoV-2 S蛋白)之mRNA用作免疫接種模型,以便研究醣位點突變之mRNA如何影響蛋白表現及免疫反應。
因此,本發明提供一種經修飾核酸分子,其編碼經修飾刺突蛋白,該經修飾刺突蛋白包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處天冬醯胺(N)成為麩醯胺酸(Q)之胺基酸取代,其中X為除脯胺酸外之任何胺基酸殘基,且S/T表示絲胺酸或蘇胺酸殘基。
經修飾核酸分子可為mRNA,或單股或雙股DNA且用作對抗病原體之免疫原或疫苗。在一個實施例中,該病原體係CoV。CoV之實例包括但不限於SARS-CoV、MERS-CoV及SARS-CoV-2。SARS-CoV-2之實例包括但不限於α-SARS-CoV2、β-SARS-CoV2、γ-SARS-CoV2、δ-SARS-CoV2及ο-SARS-CoV2及其變種。
與武漢病毒株及δ病毒株之野生型刺突蛋白(諸如SEQ ID NO: 2、16、18及20)相比,本文所描述之經修飾刺突蛋白包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處之胺基酸缺失或添加,以消除N鍵聯聚醣序列子。或者,本文所描述之經修飾刺突蛋白包含一或多個在O鍵聯醣基化位點處S/T成為丙胺酸(A)之胺基酸取代,以消除O鍵聯醣基化位點。
冠狀病毒刺突蛋白之mRNA可用作冠狀病毒疫苗,其在受體結合域(RBD)、次單元1 (S1)或次單元2 (S2)域或其變種中具有一或多個醣位點之突變。
如本文所描述之CoV或其變種之突變可為缺失、添加或取代。在一些實施例中,冠狀病毒刺突蛋白mRNA具有RBD、S1或S2中之醣位點的一或多個突變,其中具有一或多個N成為Q或S/T成為A或其組合之置換。N-醣位點之突變為將推定序列子N-X-S/T變為Q-X-S/T,及/或將O-醣位點之S/T變為A。
具有N成為Q置換之醣位點包括但不限於以下:
S-(deg-RBD),其為RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A的S蛋白(諸如SEQ ID NO: 4、22、24或26);
S-(deg-S2),其為S2中之所有9個醣位點由N突變為Q的S蛋白(諸如SEQ ID NO: 6、28、30或32);
S-(deg-S2-1194),其為除醣位點1194外,S2中之8個醣位點由N突變為Q的S蛋白(諸如SEQ ID NO: 8或34);
S-(deg-RBD-801),其為RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點801由N突變為Q的S蛋白(諸如SEQ ID NO: 10或36);
S-(deg-RBD-1194),其為RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點1194由N突變為Q的S蛋白(諸如SEQ ID NO: 12或38);及
S-(deg-RBD-122-165-234),其為RBD中之所有2個N-醣位點由N突變為Q及2個O-醣位點由S/T突變為A,及醣位點122、165及234由N突變為Q之S蛋白(諸如SEQ ID NO: 14或40)。
在另一實施例中,S-(deg-RBD)之mRNA或DNA具有SEQ ID NO: 3、21、23或25之序列,S-(deg-S2)之mRNA或DNA具有SEQ ID NO: 5、27、29或31之序列,S-(deg-S2-1194)之mRNA或DNA具有SEQ ID NO: 7或33之序列,S-(deg-RBD-801)之mRNA或DNA具有SEQ ID NO: 9或35之序列,S-(deg-RBD-1194)之mRNA或DNA具有SEQ ID NO: 11或37之序列,S-(deg-RBD-122-165-234)之mRNA或DNA具有SEQ ID NO: 13或39之序列。
本發明提供包含啟動子、5'非轉譯區、3'非轉譯區、具有或不具有S-2P之表現質體及聚(A)尾信號序列的線性DNA,其中在表現質體上推定序列子N-X-S/T變為Q-X-S/T,且O-醣位點自S/T變為A。在一個實施例中,S-2P表現質體包含SARS-CoV-2之S基因,其編碼具有K968及V969之脯胺酸取代的S的融合前狀態。
可藉由使用包含經修飾核酸分子之載體及包含如本文所描述之載體的宿主細胞,自上述DNA進行活體外轉譯來製備mRNA。目標刺突蛋白基因以合成方式製造且插入質體或小型DNA環狀片段中。質體用於mRNA疫苗生產,因為其易於複製(拷貝)且可靠地含有目標基因序列。質體DNA之兩股分離。接著,RNA聚合酶(自DNA轉錄RNA之分子)使用刺突蛋白基因產生單一mRNA分子。最後,其他分子分解質體之其餘部分以確保僅將mRNA包裝為疫苗。此過程之速度及效率可在短時段內製造大量mRNA。
本發明已發現,免疫接種所有N-醣位點處之聚醣修剪為N-乙醯基葡糖胺(GlcNAc),作為單GlcNAc裝飾S蛋白質(S
mg)之野生型S蛋白誘發對抗相關變種(包括α、β、γ、δ及ο變種)之廣泛保護性抗體及CD4
+以及CD8
+T細胞反應。進一步研究顯示S蛋白上之大部分保守抗原決定基位於RBD及S2次單元之HR2域中,但此等保守抗原決定基大部分由聚醣屏蔽以避開免疫反應。因此,移除受屏蔽之聚醣將暴露更多保守之抗原決定基且誘發更廣泛且更強的免疫反應。本發明亦使用單B細胞技術篩選來自S
mg免疫接種小鼠之B細胞以鑑別廣泛中和單株抗體,該抗體靶向RBD中之高度保守區域,未在經充分醣基化S蛋白之免疫接種中誘發,進一步表明自S蛋白移除聚醣屏蔽為研發對抗SARS-CoV-2變種之廣泛保護性疫苗的有效策略。為了將此發現轉變為mRNA疫苗設計,此處吾人聚焦於SARS-CoV-2刺突蛋白mRNA之研究,其具有RBD、S1或S2中之特定醣位點之突變或其組合,其中N置換成Q或S/T置換成A,及聚焦於其蛋白表現及免疫反應以及保護之廣度的研究。
此類mRNA之免疫接種引起摺疊異常之刺突蛋白在內質網中積聚,且引起BiP/GRP78、XBP1及p-eIF2α之上調,以誘發細胞凋亡及CD8 T細胞反應。另外,與S2-醣位點缺失之mRNA疫苗一起培育之樹突狀細胞(DC)提高第I類主要組織相容複合體(MHC I)表現。此外,移除影響刺突蛋白之穩定性、減少抗體產生及增強CD8+ T細胞反應的醣位點。本發明提供使用表現蛋白作為抗原則將無法達成之廣譜mRNA疫苗。
mRNA
奈米簇及奈米粒子
在一個態樣中,本發明提供一種mRNA奈米簇,其包含在脂質奈米粒子中調配之如本文所描述之mRNA疫苗。
可生物降解之脂質奈米粒子可用作該脂質奈米粒子。在一個實施例中,可生物降解之脂質奈米粒子為基於胍之聚合物。
在另一實施例中,本發明提供一種mRNA奈米簇,其包含囊封有本文所描述之mRNA疫苗之可生物降解脂質奈米粒子,其中可生物降解脂質奈米粒子包含基於胍及兩性離子之單元,其中基於胍及兩性離子之基團連接至聚合物之脂質尾,且其中基於胍之基團黏附於mRNA,由此在胍鎓基團與mRNA中之磷酸根之間形成鹽橋。基於胍之聚合物的實例包括但不限於如本文所描述之P1、P2、P3、Pb及Pz。
本發明提供基於胍之脂質奈米粒子作為用於mRNA奈米疫苗調配物之載劑。聚合物產生mRNA至抗原呈現細胞之高效遞送,顯示出強大的胞內體逃逸能力。相較於其他不可降解奈米載劑,聚(二硫化物)藉由胞內麩胱甘肽的及時降解亦使細胞毒性降至最低。
在另一實施例中,mRNA奈米簇具有約10或約20之奈米粒子/mRNA (N/P)比率。
本發明之冠狀病毒mRNA疫苗亦可連接至奈米粒子。
mRNA奈米簇及奈米粒子係尺寸在1與100奈米(nm)之間的粒子,其可用作固定配位體之基質。奈米粒子可例如為脂質奈米粒子、聚合奈米粒子、無機奈米粒子(諸如金奈米粒子)、脂質體、免疫刺激複合物(ISCOM)、類病毒粒子(VLP)或自組裝蛋白。
在一個實施例中,脂質奈米粒子調配物通常包含一或多種脂質。在一些實施例中,脂質為陽離子或可離子化脂質。在一些實施例中,脂質奈米粒子(LNP)調配物進一步包含其他組分,包括磷脂、結構性脂質、四級胺化合物及能夠降低粒子聚集之分子,例如PEG或經PEG修飾之脂質。
如本文所描述之mRNA疫苗可囊封於脂質體或聚合物囊泡中。
習知脂質體係藉由在一個步驟中形成脂質雙分子膜來製造,因此,脂質體之內膜及外膜均由同一構成組分製成係常見的。脂質體之成分的實例包括但不限於DSPC、DOTAP、DMG、聚乙二醇化DMG、膽固醇及其組合。在一個實施例中,藉由在室溫下以如本文所描述之比率混合mRNA及脂質成分來產生mRNA脂質體。
如本文所揭示,聚合物囊泡係由兩親媒性嵌段共聚物自組裝之殼體。此等兩親媒性嵌段共聚物為包含至少一個疏水性聚合物嵌段及至少一個親水性聚合物嵌段之大分子。當水合時,此等兩親媒性嵌段共聚物自組裝成殼體,使得疏水性嵌段傾向於彼此締合以最大限度地減少直接暴露於水且形成殼體之內表面,且親水性嵌段面向外,形成殼體之外表面。此等水溶性聚合物囊泡之疏水性核心可提供溶解額外疏水性分子之環境。因此,此等水溶性聚合物囊泡可充當囊封於聚合物囊泡內之疏水性分子的載劑聚合物。此外,兩親媒性嵌段聚合物之自組裝在不存在穩定劑時發生,其將另外提供膠體穩定性且防止聚集。在一個實施例中,藉由在室溫下以如本文所描述之比率混合mRNA及聚合物來產生mRNA脂質體。
疫苗、組合疫苗、疫苗組合物、方法及治療用途
如本文所描述之mRNA可單獨或與其他疫苗組合以用作疫苗。因此,本發明提供一種組合疫苗,其包含本發明之mRNA疫苗及一或多種額外疫苗。額外疫苗係選自一或多種COVID-19疫苗、流行性感冒(流感)疫苗、腺病毒疫苗、炭疽疫苗、霍亂疫苗、白喉疫苗、A或B型肝炎疫苗、HPV疫苗、麻疹疫苗、流行性腮腺炎疫苗、天花疫苗、輪狀病毒疫苗、肺結核疫苗、肺炎鏈球菌疫苗及b型流感嗜血桿菌疫苗及其任何組合。
本發明亦提供一種疫苗組合物,其包含如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子。本發明亦提供一種預防或治療冠狀病毒感染之方法,其包含向個體投與如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物。在一個實施例中,個體已感染冠狀病毒或處於感染冠狀病毒之風險下。
如本文所描述之mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物可以初始劑量及兩次、三次或四次加強劑量投與。在一些實施例中,mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物以初始劑量投與,及在初始劑量之後約一個月、約兩個月、約三個月、約四個月、約五個月或約六個月,以至少一次加強劑量投與。在一些實施例中,所提供之組合物在初始劑量之後約六個月、約七個月、約八個月、約九個月、約十個月、約十一個月或約一年以第二次加強劑量投與。
mRNA疫苗、mRNA奈米簇或mRNA奈米粒子或疫苗組合物係以一或多次劑量投與。在一個實施例中,劑量可包括或不包括5 μg至50 μg。在一些實施例中,劑量為約5 μg、10 μg、15 μg、20 μg、25 μg、30 μg、35 μg、40 μg、45 μg或50 μg。
疫苗組合物較佳包含醫藥學上可接受之疫苗、載劑或稀釋劑。疫苗組合物可使用任何適合方法調配。使用標準醫藥學上可接受之載劑及/或賦形劑之調配可使用醫藥領域中之常規方法進行。調配物之確切性質將視若干因素而定,包括待投與之疫苗及所需投與途徑。適合類型之調配物充分描述於Remington's Pharmaceutical Sciences,第19版, Mack Publishing Company, Eastern Pennsylvania, USA中。
如本文所描述之疫苗組合物或醫藥組合物可藉由任何途徑投與。適合途徑包括但不限於經鼻、靜脈內、肌肉內、腹膜內、皮下、皮內、經皮及經口/頰內途徑。
組合物可連同生理學上可接受之載劑或稀釋劑一起製備。通常,此類組合物製備為奈米粒子之液體懸浮液。奈米粒子可與醫藥學上可接受且與活性成分相容之賦形劑混合。適合賦形劑為例如水、生理食鹽水、右旋糖、甘油或其類似物及其組合。
其中載劑為液體以例如鼻用噴霧或鼻滴劑形式投與之適合組合物包括含有活性成分之水溶液或油性溶液。適合於氣溶膠投與之調配物可根據習知方法製備且可與其他治療劑一起遞送。
另外,必要時,醫藥組合物可含有少量輔助物質,諸如潤濕劑或乳化劑,及/或pH緩衝劑。
在不意欲限制本發明之範疇的情況下,下文給出根據本發明之實施例之例示性儀器、設備、方法及其相關結果。應注意,為讀者方便起見,實例中可使用標題或副標題,其決不應限制本發明之範疇。此外,本文中提出及揭示某些理論;然而,無論其正確與否,該等理論決不應限制本發明之範疇,本發明只要係根據本發明實踐即可,而不考慮任何特定理論或行動流程。
實例
材料及方法
細胞株。將人類胎腎細胞(HEK293)維持在含有10%熱滅活胎牛血清(FBS) (Thermo Scientific)及抗生素(100 U/ml青黴素G及100 gm/ml鏈黴素)之達爾伯克氏改良伊格爾氏培養基(Dulbecco's modified Eagle's medium;DMEM) (lnvitrogen, Rockville. MD)中。
抗體及蛋白質。兔抗SARS-CoV-2 S多株抗體及SARS-CoV-2全長S、S2、RBD及變種蛋白(293T細胞表現)係購自Sino Biologicals (中國北京)。小鼠單株抗β-肌動蛋白、GAPDH及兔單株抗MHCII抗體係購自Millipore。兔單株抗Na/K ATP酶獲自ABcan。小鼠單株抗SERCA2及兔單株抗MHC I抗體獲自Invitrogen。兔單株抗BiP/GRP78、XBP1及p-eIF2α抗體係購自ABclonal。藉由公司及吾人經由西方墨點法驗證所有商業抗體之特異性。為獲得去醣基化蛋白質,S、RBD、S1或S2蛋白置於暗處在37℃下在含PNGase F (Sigma)之緩衝溶液中去醣基化24小時。去醣基化之後,純化樣品且藉由西方墨點法檢查。
去醣基化 S 蛋白之 mRNA 疫苗及調配物。S之融合前狀態,SARS-CoV-2之密碼子最佳化S基因係藉由GenScript合成,且選殖於pcDNA3.1或pVax中,且在一個實施例中,藉由K968及V969之脯胺酸取代(S-2P)來穩定化S基因。構築S之可溶形式,結束於S-2P之麩醯胺酸Q1208,接著為T4纖維蛋白(摺疊子)三聚模體、凝血酶裂解位點及處於C端之6×His標籤。為了使N-醣位點突變,藉由對S-2P表現質體使用定點突變誘發,將推定序列子N-X-S/T變為Q-X-S/T,且使O-醣位點自S/T變為A。為了獲得mRNA疫苗,根據製造商的方案,藉由使用TOOLS Ultra High Fidelity DNA聚合酶(BIOTOOLS Co., Ltd., Taipei, Taiwan)以及1 μl DNA模板,在mMESSAGE mMACHINE®套組(Thermo Scientific)中在37℃下擴增含有T7啟動子、5'非轉譯區、3'非轉譯區、S-2P及聚(A)尾信號序列的線性DNA持續1小時。根據製造商的方案,mRNA藉由RNA清除套組(BioLabs)純化且儲存在-80℃下直至進一步使用。對於調配物mRNA-LNP,mRNA使用自組裝方法囊封於LNP中,其中將pH 4.0的mRNA水溶液與含有可離子化陽離子脂質、膽鹼磷脂、膽固醇及聚乙二醇脂質的乙醇脂質混合物快速混合。LNP之組合物為DSPC (Sigma)、膽固醇(Sigma)、DOTAP (Sigma)及DMG-PEG 2000 (Sigma)。表徵mRNA-LNP且隨後以1 mg/ml之濃度儲存在-80℃下。在用10 μg mRNA-LNP在培養盤之六個孔中轉染HEK293細胞之後48小時,收集全部細胞溶解物以藉由西方墨點法監測S之表現。
動物及免疫接種。6至8週齡之BALB/c小鼠(n=5)用50 μg mRNA-LNP於含300 mM蔗糖之PBS中之溶液進行肌內免疫接種。動物在第0週免疫接種,在第2週用第二次接種疫苗增強,且在加打免疫接種之後一週自各小鼠收集血清樣品及脾臟。動物實驗藉由中央研究院之實驗動物照護及使用委員會(Institutional Animal Care and Use Committee of Academia Sinica)評估及批准。
血清 IgG 效價量測。抗S蛋白ELISA用於測定IgG效價。培養盤用50 ng/孔變種S蛋白質塗佈,如圖4及圖5中所示,且隨後用5%脫脂牛奶阻斷。依序添加來自免疫接種小鼠之血清及HRP結合二次抗體。使用過氧化酶受質溶液(TMB)及1M H
2SO
4停止液,且藉由微定量盤式讀取器讀取吸光度(OD 450 nm)。
用於血清研究之假病毒中和分析。假病毒由中央研究院之RNAi Core Facility構築。簡言之,藉由用pCMV-ΔR8.91、pLAS2w.Fluc. Ppuro及pcDNA3.1-nCoV-SΔ18短暫轉染HEK-293T細胞,以產生攜載SARS-CoV-2 S蛋白或變種之假型慢病毒。在轉染前一天接種HEK-293T細胞,接著藉由TransITR-LT1轉染試劑(Mirus)將質體遞送至細胞中。培養基在轉染後16小時更新且在48小時及72小時收集。藉由離心移除細胞碎片,且使上澄液通過0.45 μm針筒過濾器(Pall Corporation)。假型慢病毒隨後儲存在-80℃下。為藉由AlarmaBlue分析(Thermo Scientific)來估算慢病毒效價,藉由使用細胞存活率分析估算假型慢病毒之轉導單位(TU)。表現人類ACE2基因的HEK-293T細胞在慢病毒轉導之前一天接種於96孔培養盤上。為測定假型慢病毒之效價,將不同量之慢病毒添加至含有凝聚胺(最終濃度8 μg/ml) (sigma)之培養基中,且在37℃下在96孔培養盤中以1,100×g進行離心感染30分鐘。培育16小時之後,移除含有病毒及凝聚胺之培養基且用含有2.5 μg/ml嘌呤黴素(sigma)之新製完全DMEM替換。嘌呤黴素處理48小時之後,移除培養基且藉由使用AlarmaBlue試劑根據製造商說明書偵測細胞存活率。未感染細胞之存活率設定為100%,且藉由存活細胞對比稀釋之病毒劑量的繪圖來測定病毒效價。
對於中和分析,將熱滅活血清或抗體以所需稀釋度連續稀釋,且與1,000 TU SARS-CoV-2假型慢病毒在37℃下在DMEM中一起培育1小時。混合物接著在96孔培養盤中用穩定表現人類ACE2基因之10,000個HEK-293T細胞接種。在感染後16小時用新製完全DMEM (補充有10% FBS及100 U/ml青黴素/鏈黴素)替換培養基且再繼續培養48小時。螢光素酶基因之表現量藉由使用Bright-Glo™ Luciferase Assay System (Promega)測定。藉由Tecan i-control (Infinite 500)偵測相對光單位(RLU)。抑制百分比計算為稀釋血清之存在下的RLU減少相對於無血清對照之RLU值的比率,且計算公式如下所示:(RLU
對照-RLU
血清)/RLU
對照。
SARS - CoV - 2 S 蛋白之資訊分析。SARS-CoV-2之1,117,474 S蛋白序列及其變種係提取自全球共用禽流感資料倡議組織(Global Initiative on Sharing Avian Influenza Database) (GISAID版本:2021年4月18日)。藉由CHARMM-GUI及OpenMM程式構築具有代表性聚醣特徵的S蛋白3D結構模型。在此研究中使用由UniProt定義之刺突蛋白的跨膜區。CHARMM-GUI之輸入內容包括PDB檔案6VSB_1_1_1、代表性聚醣特徵及參數設置。藉由FreeSASA程式計算具有或不具有代表性聚醣之刺突蛋白的相對溶劑可接近性(RSA)。在FreeSASA程式中使用探針半徑7.2 Å以模擬抗體之互補決定區(CDR)中之高變環的平均尺寸。在此研究中使用之各殘基的RSA值為來自三個蛋白鏈之平均RSA值。暴露/埋藏殘基之定義與Kajander, T.等人之研究相同。
分泌 GrzB 及 IFN γ 之細胞的量測。根據製造商說明書,在GrzB ELISpot分析(R&D Systems)中,來自免疫接種小鼠之總計5×10
5個脾細胞使用全長S、RBD及S2肽混合物(每一肽0.1 μg/ml之最終濃度) (Sino Biologicals)進行活體外再刺激,且斑點經計數。對於T細胞次型分型,根據製造商說明書,使用Dynabeads Untouched Mouse CD4及CD8細胞套組(Invitrogen),自脾細胞懸浮液分離CD8
+T細胞及CD4
+T細胞。隨後用負載有全長WT S肽混合物(0.1 μg/ml最終濃度) (Sino Biologicals)之5×10
4同基因型骨髓衍生之DC再刺激CD8
+T細胞及CD4
+T細胞(1×10
5個)。藉由流式細胞量測術測定經分離T細胞次群之純度,以計算每1×10
5個CD4
+或CD8
+T細胞之斑點計數。對於流式細胞量測術,細胞以10
6個細胞/ml之密度懸浮於FACS緩衝液[含2% (vol/vol) FBS之PBS]中,且用於此研究中之抗體為抗IFNγ (abcam)。細胞螢光強度藉由FACS Canto (BD Biosciences)及FCS Express 3.0軟體分析。
IFN γ 及其他細胞介素之量測。IFNγ、IL-2、IL-4、IL-6、IL-12及IL-13藉由使用ELISA套組根據製造商之方案(IFN-γ:Boster Biological Technology Co., Ltd;IL-2、IL-4、IL-6、IL-12及IL-13:R&D Systems)量測。
DNA 質體轉染及 MG132 處理。在HEK293細胞接種於6孔盤中之後,細胞藉由TransIT®-LT1轉染試劑(Mirus)用3 μg各質體轉染,且接著與1 μM MG-132 (MedChemExpress)或DMSO一起在37℃下培育24小時。收集全部溶解物且藉由西方墨點法分析變種S表現。
活體外轉譯。根據製造商說明書,使用人類IVT系統(Thermo)中之醣蛋白表現,利用編碼S-2P之質體進行活體外轉譯。根據製造商之方案,S蛋白在不同培育時段中之表現由SARS-CoV-2刺突蛋白ELISA套組(ABclonal)監測。
未摺疊蛋白反應之偵測。利用TransIT®-mRNA轉染套組(Mirus)用10 μg S mRNA轉染HEK293細胞48小時之後,根據製造商之方案,藉由Minute™ ER富集套組(Invent Biotech)分離質膜及ER。藉由西方墨點法分析質膜、胞溶質及ER中之S蛋白。收集全部溶解物且藉由西方墨點法監測UPR標記XBP1、BiP/GRP78及p-eIF2α。根據製造商說明書,藉由APO™-BrdU TUNEL分析套組(Thermo)量測凋亡細胞。
S - 2P 表現的可溶形式。利用TransIT®-mRNA轉染套組(Mirus)用10 μg編碼變種S-2P之可溶形式的mRNA轉染HEK293細胞持續72小時,使用Ni-NTA親和管柱(GE Healthcare)自細胞上澄液純化S蛋白。藉由西方墨點法監測經純化之蛋白質及全部溶解物之S的蛋白含量。
mRNA 疫苗誘發 DC 上之 MHC I / II 表現。遵循來自公司之程序,藉由使用M-pluriBead細胞分離套組(pluriSelect)自小鼠分離DC,且在37℃下與10 μg mRNA-LNP一起在DC培養基(RPMI 1640,其補充有20 ng/mL鼠類GM-CSF (R&D Systems)、10% FBS、50 μM 2-ME、100單位/mL青黴素及100 μg/mL鏈黴素)中培育48小時,隨後藉由流式細胞量測術分析MHC I及MHC II表現。
統計及再現性。所有資料均呈現為平均值±平均值標準誤差。實驗之樣本數及重複數展示在圖例中。使用學生t檢定(Students t test)確定各組之間的比較。在*P<0.001、**P<0.05時,差異視為顯著。所有資料均使用GraphPad Prism 6軟體分析。
實例 1 : S 蛋白之醣基化影響抗體產生
作為吾等努力鑑別可能保守抗原決定基作為用於抗體研發及下一代疫苗設計,且用於設計具有廣泛保護性免疫反應之通用疫苗之目標的一部分,吾等對SARS-CoV-2 S蛋白之218,516個可用序列進行S蛋白突變分析。S蛋白具有1,273個胺基酸,且在分析之218,516個序列中,存在1,149個可變胺基酸位置,包括S1域(672個胺基酸)中之613個、S2域(588個胺基酸)中之524個及RBD (152個胺基酸)中之134個;然而,突變率在1,076個位點處小於0.1%,同時在73個位點處大於0.1%。保守序列可見於S1、S2及RBD區域中,且最長序列來自靠近S2區域中之HR1域的R983至I1013。所有22個N-醣基化位點均在SARS-CoV-2變種中高度保守。更多序列(約600萬)之進一步分析顯示保守抗原決定基之類似分佈,其中7個在RBD中且5個在HR2中,且10個保守抗原決定基由聚醣屏蔽(圖1)。吾等咸信移除病毒表面醣蛋白上之聚醣屏蔽以暴露更多保守抗原決定基為對抗SARS-CoV-2之疫苗設計的極有效且通用的方法。由於連接至Asn之單個GlcNAc殘基係醣蛋白摺疊及穩定化所需之
N-聚醣的最小組分,因此假定修剪
N-聚醣使單個GlcNAc留在SARS-CoV-2 S蛋白上將不影響其摺疊,但將促進蛋白主鏈最大暴露以誘發穩固且蛋白質特異性免疫反應,同時維持其結構完整性。
基於吾人之初步結果,經充分醣基化(未經修飾)及經單GlcNAc裝飾(在所有
N-醣位點上)全長S、S1、S2及RBD用作免疫接種研究之免疫原。吾人製造的S、S1、S2及RBD次單元保留如上文所描述之吾等初步研究中發現之必需醣位點,且缺失特定醣位點,且其單GlcNAc裝飾變種作為免疫接種之免疫原。測試抗血清與代表性S蛋白變種的相互作用及對抗假病毒介導感染之中和活性,且進一步研究具有廣泛保護活性之抗血清,包括抗原決定基定位及對CD4
+及CD8
+T細胞反應之佐劑效應。單GlcNAc裝飾變種係藉由移除全長S、S1、S2及RBD之
N-醣位點上的異質聚醣層來製造,該等域係使用更通用且良好展現之CHO、HEK293或Gnt1-缺失型HEK293細胞株表現系統生成。此等細胞株中S蛋白表現之聚醣可經內切糖苷酶修剪,以產生在所有N-醣基化位點處具有單GlcNAc之所需蛋白質,及來自後者(Gnt1-缺乏型HEK293)之聚醣為高甘露糖類型,且可使用內切糖苷酶H (Endo-H)消化以產生在所有
N-醣基化位點處具有單GlcNAc之所需蛋白質。因為O-聚醣對病毒進入至關重要,所以不進行修飾;但必要時,其可藉由外切糖苷酶之混合液來修剪。研究此單GlcNAc裝飾全長及截短S蛋白之結構完整性。含有充分醣基化及單GlcNAc蛋白質以及經醣位點改造之S蛋白(藉由用Gln置換Asn,如反向遺傳學研究中所示)的免疫原用於小鼠免疫接種,以鑑別以廣泛中和活性靶向S蛋白上之各種域的抗體。藉由充分及單GlcNAc裝飾以及經醣位點改造之S蛋白及其截短形式檢查血清抗體之特異性。此外,使用具有或不具有單GlcNAc裝飾之一系列合成肽或自單GlcNAc裝飾S蛋白之蛋白酶消化獲得的糖肽,在具有人類化ACE2受體之轉殖基因小鼠中研究結合特異性及CD8
+T細胞反應。使用吾等實驗室中研發之假病毒中和分析進一步評估免疫接種小鼠血清之中和活性。圖2顯示N-及O-醣位點之鑑別及變種中之突變。所有24個醣位點在600萬S蛋白序列中高度保守。
S蛋白常常突變,且22個N-及2個O-醣位點(RBD中2個N-及2個O-醣位點,及S2中6個N-醣位點)高度醣基化,以避開宿主免疫反應(圖16)。為了研究具有突變醣位點的S蛋白之mRNA疫苗是否影響及如何影響S蛋白表現及免疫反應,吾等分別在mRNA之RBD或S2區域中突變多個N-醣位點(N-X-S/T序列子中N突變為Q)及O-醣位點(S/T突變為A)。在確認變種融合前S蛋白於HEK293細胞株中之表現之後(圖3),將編碼S蛋白或具有醣位點突變之S蛋白的mRNA囊封於LNP中以形成mRNA-LNP,用於在小鼠中免疫接種。來自經過mRNA(mRNA中所有S2 N-醣位點發生突變(S-(deg-S2))或除N-1194外所有S2 N-醣位點發生突變(S-(S2-1194)))免疫之小鼠的血清,在ELISA分析中顯示與未經修飾之mRNA相比較,針對完全醣基化WT S蛋白(圖4A)、S2 (圖4B)、RBD (圖4C)或去醣基化S蛋白(圖4D)之較低IgG效價,但針對去醣基化S2抗原(圖4E)具有較高IgG效價。然而,經過缺失所有RBD醣位點之mRNA (S-(deg-RBD))免疫之小鼠針對完全醣基化RBD引發之IgG效價則略微降低,但識別去醣基化RBD抗原(圖4F)之IgG效價較高,表示S蛋白上之醣基化會影響抗體之產生及其結合特異性。另外,使用S-(deg-RBD)、S-(deg-S2)或S-(S2-1194) mRNA之免疫接種會針對α (圖5
A)、β (圖5
B)、γ (圖5
C)、δ及ο變種(圖5
D)誘發較高IgG效價,表示S蛋白之醣基化會調節由mRNA疫苗產生之抗體的特異性。為了分析醣位點突變對由免疫接種小鼠產生之抗體的中和活性的影響,進行假病毒中和分析且結果顯示,相較於WT,RBD或S2中缺失醣位點之mRNA疫苗產生的抗體對抗WT假病毒之中和活性降低(圖5),但對抗四個相關變種的中和活性較佳(圖6及表1)。為了進一步理解此觀察結果,序列分析揭露RBD或S2中之醣位點的突變暴露更多保守的抗原決定基,以引發免疫反應(圖6),且RBD及S2域含有S蛋白中之大部分高度保守序列(RBD中7個,S2之HR2中5個)。此等結果表示,S蛋白疫苗之mRNA中某些醣位點之突變將影響抗體之產生及其特異性以及免疫反應。
武漢病毒株之
S
-(
deg
-
S2
)
的
DNA
或
RNA
序列
(
自
5
'
端至
3
'
端
)
:
武漢病毒株之
S
-(
deg
-
S2
)
的蛋白質序列
(
自
N
端至
C
端
)
:
武漢 S - 2P 病毒株之 S -( deg - RBD - 122 - 165 - 234 ) 的蛋白質序列 ( 自 N 端至 C 端 ) : 表1:變種假病毒中和分析之IG
50。
實例 5 : 醣基化影響細胞及細胞介素反應
IC 50 血清稀釋度 | WT | B.1.1.7 | B.1.351 | P1 | B.1.617.2 |
WT | 7658.4 | 1250.1 | 710.6 | 776.5 | 835.7 |
S-(deg-RBD) | 6496.2 | 1926.5 | 1108.3 | 1523.6 | 1868.3 |
S-(deg-S2) | 4825.6 | 4035.9 | 4568.3 | 4235.3 | 4786.3 |
S-(S2-1194) | 5767.8 | 4628.6 | 5287.5 | 4989.6 | 5103.4 |
為了表徵T細胞反應,來自免疫接種小鼠之脾細胞經分離,且與S蛋白之肽池一起培育以藉由elispot分析量測分泌顆粒酶B (GrzB)之T細胞。顯示在與全長WT S (圖7
A)、RBD (圖7
B)及S2肽(圖7
C)一起培育後,S-(deg-S2)及S-(S2-1194)誘發比WT及S-(deg-RBD)更多的分泌GrzB之細胞,表明S2上之醣基化調節T細胞反應。為進一步研究對CD4
+及CD8
+T細胞之影響,將經分離之T細胞與骨髓衍生之樹突狀細胞(DC)及WT S肽池一起培育,以藉由流式細胞量測術量測分泌IFNγ之T細胞。所有經疫苗接種小鼠中之分泌IFNγ之CD4
+T細胞的數目無顯著差異(圖7
D),但S-(deg-S2)或S-(S2-1194)之mRNA疫苗誘發更多分泌IFNγ之CD8
+T細胞,表明S2中之醣基化調節CD8
+T細胞反應(圖7
E)。
為了分析細胞介素表現,來自與全長WT S肽池一起培育之脾細胞的培養基藉由ELISA量測。顯示來自S-(deg-S2)及S-(S2-1194)免疫接種小鼠之脾細胞分泌較高含量之T輔助1 (TH1)細胞介素(IFNγ、IL-2及IL-12) (圖8A、B及E),而來自WT及S-(deg-RBD)免疫接種小鼠之脾細胞分泌較高含量之T輔助2 (TH2)細胞介素(IL-4、IL-6及IL-13) (圖8C、D及F)。總體而言,具有醣位點突變之所有RNA疫苗引發抗體及CD4
+及CD8
+T細胞反應以及相關細胞介素,其中在經S-(deg-S2)及S-(S2-1194)免疫之小鼠中具有更強的產生IFNγ之CD8
+T細胞反應。此等結果表明,S2上之醣基化調節T細胞反應及細胞介素表現。
實例 6 : S2 上之去醣基化誘發未摺疊蛋白反應
為了研究S2上之醣基化如何影響免疫反應,HEK293細胞經變種之融合前穩定S蛋白表現質體轉染。其顯示S-(deg-S2)及S-(S2-1194)並不表現良好,但S-(deg-S2)及S-(S2-1194)蛋白質之含量在用MG132 (蛋白酶體抑制劑)處理之後得到一定程度恢復(圖9)。活體外轉譯分析顯示,mRNA序列中之醣位點的突變不影響轉譯效率(圖10)。此等結果表明自S2移除醣基化會引起活體內轉譯蛋白質之降解。為了研究移除S2上之醣基化是否導致摺疊異常或未摺疊蛋白質之表現,分離質膜及內質網(ER)以檢查S蛋白之分佈,此係由於摺疊異常或未摺疊之S蛋白可在ER堆疊以再摺疊或經由ER相關降解破壞。在用mRNA轉染HEK293細胞之後48小時,質膜、胞溶質及ER中存在所有變種S蛋白。然而,質膜中存在更多WT及S-(deg-RBD)之蛋白,而ER中存在更多S-(deg-S2)及S-(S2-1194)之蛋白(圖11)。另外,HEK293細胞經編碼S-(deg-S2)及S-(S2-1194)蛋白之可溶融合前形式的mRNA轉染,無法分泌至培養基(圖16),表明S2中之去醣基化影響S蛋白之摺疊。由於ER中增加的未摺疊S蛋白將觸發未摺疊蛋白反應(UPR),因此在48小時檢查經RNA轉染之HEK293細胞中的UPR標記蛋白BiP/GRP78、XBP1及p-eIF2α。結果顯示,經S-(deg-S2)及S-(S2-1194)轉染細胞中,BiP/GRP78及XBP1上調,且p-eIF2α之含量強於WT及S-(deg-RBD)組(圖12)。另外,移除S2上之醣基化誘發的凋亡細胞多於WT及S-(deg-RBD)所誘發(圖13),表明S2之去醣基化誘發高於WT及S-(deg-RBD)蛋白之ER壓力水準,且S2上之醣基化影響蛋白質摺疊以調節UPR之表現。
實例 7 : S2 上之醣基化影響樹突狀細胞 ( DC ) 上之 MHC I 表現。
為研究UPR是否導致偏向性免疫反應,藉由流式細胞量測術來量測DC上之第I類主要組織相容複合體(MHC I)及第II類主要組織相容複合體(MHC II),其對於在加工之後呈現內化分子為必需的。在DC與mRNA疫苗之變種一起培育之後,MHC I/II在所有疫苗中上調,且S-(deg-S2)或S-(S2-1194)之mRNA疫苗誘發之MHC I表現DC多於WT及S-(deg-RBD) (圖14及圖17),表明UPR調節DC上之MHC I表現。
實例 8 : 刺突蛋白中之醣位點影響 S 蛋白之穩定性且隨後影響 CD8 + T 細胞反應。
為了研究哪些醣位點調節宿主免疫反應,吾人使用S-(deg-RBD)疫苗作為模型系統,因為其誘發之抗體量與WT類似且具有比WT更好的對抗四種相關變種之中和活性。此處,吾人移除RBD醣位點及S2中之醣位點N-801 (S-(deg-RBD-801))或醣位點N-1194 (S-(deg-RBD-1194)),此係由於此等醣位點涉及S蛋白表現,尤其與S蛋白完整性及其結合親和力有關之醣位點N-1194。由於醣位點N-122、N-165及N-234調節RBD之結構且影響抗體之中和活性,因此吾等移除此等醣位點以形成S-(deg-RBD-122-165-234)疫苗(圖15)。在用變種之融合前穩定S蛋白表現質體轉染HEK293細胞之後,顯示S-(deg-RBD-801)及S-(deg-RBD-122-165-234)未表現良好且S-(deg-RBD-1194)顯著降低蛋白質表現,但在用MG132處理之後,此等蛋白質變種之含量得到一定程度恢復,表明疫苗之變種誘發經轉譯蛋白質之降解(圖21
A)。在確認變種融合前S蛋白之表現在HEK293細胞株中形成mRNA-LNP之後(圖21
B),用不同疫苗使小鼠免疫。顯示在ELISA分析中與未經修飾之mRNA相比,S-(deg-RBD-801)、S-(deg-RBD-1194)及S-(deg-RBD-122-165-234)誘發針對完全醣基化WT S (圖18A)及RBD蛋白(圖18B)之較低IgG效價,但S-(deg-RBD-801)及S-(deg-RBD-122-165-234)具有針對去醣基化RBD抗原(圖18C)之較高IgG效價,表明此等醣位點上之醣基化調節抗體產生。為了分析免疫接種小鼠產生之抗體的中和活性,假病毒中和分析顯示,相較於WT,S-(deg-RBD-801)、S-(deg-RBD-1194)及S-(deg-RBD-122-165-234) mRNA疫苗產生的抗體對抗WT假病毒之中和活性降低(圖19),但具有對抗四個相關變種的中和活性較好(圖19及表2)。
表2:變種假病毒中和分析之IG
50。
IC 50 血清稀釋度 | WT | B.1.1.7 | B.1.351 | P1 | B.1.617.2 |
WT | 7430.8 | 1024.5 | 680.4 | 790.4 | 880.4 |
S-(deg-RBD-801) | 5020.6 | 2680.4 | 1098.5 | 1640.5 | 1850.5 |
S-(deg-RBD-1194) | 3480.5 | 1120.5 | 780.5 | 910.6 | 1040.3 |
S-(deg-RBD-122-165-234) | 5240.8 | 3168.8 | 1820.8 | 2140.5 | 2040.5 |
為了表徵T細胞反應,免疫接種小鼠之脾細胞與S、RBD及S2蛋白之肽池一起培育,接著藉由elispot分析量測分泌顆粒酶B (GrzB)之T細胞。顯示S-(deg-RBD-801)、S-(deg-RBD-1194)及S-(deg-RBD-122-165-234)在所有肽池中誘發比WT更多之分泌GrzB之T細胞,尤其S-(deg-RBD-1194)所誘發(圖20及圖22A、圖22B)。經分離CD4
+及CD8
+T細胞與骨髓衍生之DC及WT S肽池一起培育,以藉由流式細胞量測術量測分泌IFNγ之T細胞之後,所有經疫苗接種小鼠中之分泌IFNγ之CD4
+T細胞的數目無顯著差異(圖22
C),但S-(deg-RBD-801)、S-(deg-RBD-1194)及S-(deg-RBD-122-165-234) mRNA疫苗誘發更多分泌IFNγ之CD8
+T細胞,表明此等疫苗誘發更強之CD8
+T細胞反應(圖20)。總體而言,S-(deg-RBD-801)、S-(deg-RBD-1194)及S-(deg-RBD-122-165-234)降低質體系統中之蛋白質表現量,且誘發較少抗體,但提高CD8
+T細胞反應,尤其S-(deg-RBD-1194)所提高。此等結果表明,與S之摺疊或穩定性有關之醣位點上的醣基化調節宿主免疫反應。
實例 9 : 基於胍之聚 ( 二硫化物 ) 的設計及合成。
吾人設計一系列聚合物及連接至脂質尾之基於胍及/或兩性離子之頭基,且研究其遞送刺突蛋白mRNA之能力。如圖23中所示,含有胍基團之傳播子P1及多價呈現傳播子P2藉由在胍鎓與mRNA中磷酸根之間形成強鹽橋來促進mRNA與聚合物之黏著。一旦經聚合物囊封之mRNA到達細胞質,二硫化物連接子可藉由細胞內麩胱甘肽降解以釋放mRNA。另外,經降解之二硫化物單體亦藉由避免高分子量聚合物在細胞內部之積聚而降低細胞毒性。
為製備聚合物,含有單胍之二硫化物單體根據先前報導之程序合成(
Gasparini , G .; Bang , E .- K .; Molinard , G .; Tulumello , D . V .; Ward , S .; Kelley , S . O .; Roux , A .; Sakai , N .; Matile , S ., J . Am . Chem . Soc . 2014 , 136 , 6069 - 6074),且三胍二硫化物單體由氮基三乙酸連接基團合成以呈現三聚胍單體。在胍基團旁側含有兩個應變二硫化物之傳播子
Pb經設計以形成聚合物之分支組態。傳播子
P3及
Pz經設計為間隔子,其可有助於經包覆分子自胞內體逸出。
圖24描繪引發劑(I0)、傳播子(P1、P2)及聚合/解聚合過程之經設計結構。
在室溫下於脫氣水溶液中進行
P1、
P2、
P3及
Pb之聚合。簡言之,在5 mM引發劑
1及200 mM傳播子
P存在於1 M pH 7 TEOA緩衝液中之情況下,劇烈攪拌30分鐘。藉由添加0.5 M碘乙醯胺進行終止。為篩選用於高效胞內遞送mRNA之最佳聚合物,進行不同傳播子之共聚合,且其囊封能力及轉染效率由編碼GFP之mRNA在HEK293T細胞中評估。共聚物(
P1 / P3)及(
P2 / P3)以2:1之比製備,(
P1 / Pb)及(
P2 / Pb)以4:1之比製備。
為了篩選最佳聚合物以實現mRNA之最佳囊封及高效胞內遞送,檢驗8種類型之合成均聚物及雜-共聚物囊封GFP mRNA之能力。如圖25A中所示,所有具有胍基團之共聚物能夠以N/P比率=10抑制GFP mRNA之遷移。特定言之,具有三胍部分之
P2 / P3及
P2 / Pb共聚物產生較高的與mRNA複合之能力,其與由傳統使用之轉染劑聚乙亞胺(PEI)介導之結果相當。藉由TEM成像,所得奈米簇
P2 / P3-mRNA複合物之平均尺寸為約90 nm (圖25B)。另外,分支聚合物
P1 / Pb及
P2 / Pb亦展示類似的囊封mRNA之能力。分支胍鎓由於其對功能材料之良好可接近性及可撓性而受到關注。
接下來,吾人藉由使用不同共聚物評估HEK293T細胞中GFP-mRNA之轉染效率。首先,吾人發現P1/P3共聚物在N/P=10下展現良好的轉染mRNA之能力,其比單獨P1或P3及PEI更高效(圖26A)。結果指示P1或P3聚合物不利於胞內遞送,而雙官能共聚物P1/P3極佳轉染mRNA。藉由與二乙三胺間隔基共聚,胍基團之隨機間隔可適合於符合核苷酸之磷酸鹽電荷。吾人隨後研究不同共聚物對轉染活性之影響。在圖26B中,P2/P3之組合展示提高之GFP表現,表明三胍基團增強mRNA囊封且一旦遞送至細胞質亦可釋放mRNA。然而,儘管藉由使用P2/Pb完成與mRNA之完全複合,但分支聚(二硫化物) P1/Pb及P2/Pb未顯示令人滿意的mRNA負荷釋放(圖26A)。吾等利用出色的共聚物P2/P3進一步最佳化N/P比率(1、5、10及20)。發現轉染之最佳效能為10 (圖26C)。
基於GFP mRNA之結果,製備野生型刺突蛋白mRNA且藉由聚Gu以不同N/P比率囊封(圖27)。聚Gu顯示良好的中和刺突蛋白mRNA電荷之能力,且在N/P比率為1時成功地捕獲其。
隨後,吾人在HEK293T細胞中轉染刺突蛋白mRNA且進行西方墨點法。HEK293T細胞經3 μg刺突蛋白mRNA轉染。轉染後48小時,使用刺突蛋白特異性抗體經由西方墨點法分析細胞之刺突蛋白表現。結果顯示約250 kDa處之SARS-Cov-2刺突蛋白之顯著帶,且採用含有刺突蛋白mRNA之PBS緩衝液作為陰性對照(圖28),其證明聚Gu作為活體外mRNA轉染之奈米載劑的可行性。另外,聚Gu在高達10 μg (50 μg/mL)時不展現任何明顯細胞毒性(圖29)。而脂質奈米粒子(LNP)展現對具有高複合物負載之細胞高得多的毒性。
總之,吾人研發一系列聚(二硫化物)且展現胍基及兩性離子間隔基之組合用於活體外mRNA遞送之極高效率。在胞內麩胱甘肽下,藉由應變二硫化物經由硫醇介導之吸收路徑的高效胞內遞送為可裂解的。此外,針對SARS-Cov-2,與常用之LNP相比,聚合物之分解亦使細胞毒性降至最低。
本說明書中所引用之所有公開案及專利申請案以引用的方式併入本文中,就如同各個別公開案或專利申請案特定地且個別地指示以引用的方式併入一般。
儘管已出於清楚理解之目的藉由說明及實例相當詳細地描述前述發明,但根據本發明之教示,一般熟習此項技術者將顯而易見,可在不背離隨附申請專利範圍之精神或範疇之情況下對其進行某些變化及修改。
以下圖式形成本說明書的一部分且被包含在內以進一步展示本發明之特定態樣,其中本發明可藉由結合本文中呈現之特定實施例的詳細描述並參考此等圖式中之一或多者而得到較佳理解。
圖1. S蛋白變種之保守抗原決定基,其中10個經聚醣屏蔽。
圖2.鑑別變種中之N-及O-醣位點及突變。所有24個醣位點在600萬個S蛋白序列中高度保守。
圖3.藉由西方墨點法來分析在用mRNA轉染之後48小時的S蛋白表現。用抗S及抗β-肌動蛋白單株抗體探測濾膜。
圖4A至圖4F. BALB/c小鼠中之體液免疫反應展示為藉由ELISA分析之抗S WT (A)、S2 (B)、RBD (C)、去醣基化S (D)、去醣基化S2 (E)及去醣基化RBD (F)血清蛋白質特異性IgG終點效價。五次獨立實驗之平均值±SD。*P<0.001。
圖5A至圖5D.醣基化調節受引發之抗體的特異性且影響mRNA疫苗保護之廣度。藉由ELISA測定α (
A)、β (
B)、γ (
C)及δ (
D) S蛋白特異性IgG抗體終點效價。五次獨立實驗之平均值±SD。*P<0.001,**P<0.05。
圖6A至圖6F.假病毒變種之中和曲線展示於WT (
A)、α (
B)、β (
C)、γ (
D)、δ (
E)及ο (
F)中。五次獨立實驗之平均值±SD。*P<0.001,**P<0.05。
圖7A至圖7E.醣基化影響CD8
+T細胞反應。自經免疫接種小鼠分離之脾細胞與全長WT S (
A)、RBD (
B)及S2 (
C)肽池一起培育,接著藉由Elispot量測分泌GrzB之細胞。分離出CD4
+(
D)及CD8
+(
E) T細胞且與骨髓衍生之樹突狀細胞及全長WT S肽池一起培育,以藉由流式細胞量測術量測分泌IFNγ之T細胞。(
A-
E)五次獨立實驗之平均值±SD。*P<0.001。
圖8A至圖8F.醣基化影響細胞介素產生。自免疫接種mRNA疫苗之小鼠分離的脾細胞與全長WT S肽池一起培育之後,量測(
A) INFγ、(
B) IL-2、(
C) IL-4、(
D) IL-6、(
E) IL-12及(
F)
IL-13。
( A - F )五次獨立實驗之平均值±SD。
*P<0.001,**P<0.05。
圖9. mRNA中之醣位點的缺失產生去醣基化S蛋白及未摺疊之蛋白反應。藉由西方墨點法,經由經質體轉染之HEK293T細胞及MG132處理,分析去醣基化S蛋白表現。用抗S及抗GAPDH單株抗體探測濾膜。
圖10.藉由ELISA監測如圖中所示之不同培育時間之活體外轉譯去醣基化S變種。三次獨立實驗之平均值±SD。*P<0.001。
圖11A至圖11C.在用mRNA疫苗轉染HEK293細胞之後48小時,分離質膜(
A)、胞溶質(不含ER) (
B)及ER (
C)以藉由西方墨點法分析S蛋白之量。用抗S、抗Na/K ATP酶、抗SERCA2及抗GAPDH單株抗體探測濾膜。
圖12.在用去醣基化S蛋白變種之mRNA疫苗轉染HEK293細胞之後48小時,藉由西方墨點法對UPR標記蛋白BiP/GRP78、XBP1及p-eIF2α之分析。用抗BiP、抗XBP1、抗p-eIF2α及抗β-肌動蛋白單株抗體探測濾紙。
圖13.在HEK293細胞用mRNA疫苗轉染之後如圖中所示之不同時間時,經由APO-BrdU TUNEL分析對凋亡細胞進行分析。三次獨立實驗之平均值±SD。* P<0.001。
圖14.在與mRNA疫苗之變種一起培育之後,藉由流式細胞量測術分析DC之MHC I表現。三次獨立實驗之平均值±SD。*P<0.001。
圖15A至圖15G. SARS-CoV-2刺突蛋白及疫苗設計之示意性表示:WT (
A);S-(deg-RBD) (
B);S-(deg-S2) (
C);S-(deg-S2-1194) (
D);S-(deg-RBD-801) (
E);S-(deg-RBD-1194) (F);S-(deg-RBD-122-165-234) (G)。NTD為N端域(14至305殘基)。RBD為受體結合域(319至541殘基)。FP為融合肽(788至806殘基)。HR1為七肽重複序列1 (912至984殘基)。HR2為七肽重複序列2 (1163至1213殘基)。TM為跨膜域(1213至1237殘基)。CT為細胞質域(1237至1273殘基)。S2次單元(686至1273殘基)。2P,(K986P及V987P)。Ψ為N-醣基化位點;φ為O-醣基化位點。
圖16. S2上之醣基化調節可溶性融合前SARS-CoV-2刺突蛋白之分泌。在用編碼可溶性融合前形式之變種S的mRNA疫苗轉染HEK293細胞之後,藉由西方墨點法確定S之位置。用抗S及抗GAPDH單株抗體探測濾膜。
圖17.mRNA疫苗影響DC上之MHC II表現。在與mRNA疫苗之變種一起培育之後,藉由流式細胞量測術分析DC之MHC II表現。三次獨立實驗之平均值±SD。* P<0.001。
圖18A至圖18C.來自特定醣位點缺陷之S mRNA疫苗的免疫反應表徵。BALB/c小鼠中之體液免疫反應展示為來自血清之針對S WT (
A)、RBD (
B)及去醣基化RBD (
C)之蛋白質特異性IgG效價,其藉由ELISA分析。
圖19A至圖19E.來自特定醣位點缺陷之S mRNA疫苗的免疫反應表徵。假病毒變種之中和曲線展示於WT (
A)、α (
B)、β (
C)、γ (
D)及δ (
E)中。
圖20A至圖20B.來自特定醣位點缺陷之S mRNA疫苗的免疫反應表徵。(
A)自經免疫接種小鼠分離之脾細胞與全長WT S肽池一起培育之後,藉由Elispot量測分泌GrzB之細胞。(
B)分離出來自經免疫接種小鼠之CD8
+T細胞且與骨髓衍生之DC及全長WT S肽池一起培育,以藉由流式細胞量測術量測分泌IFNγ之T細胞。(A-J)五次獨立實驗之平均值±SD。*P<0.001。
圖21A及圖21B.特定醣位點缺陷S之蛋白表現量(
A)藉由西方墨點法,經由經質體轉染之HEK293T細胞及MG132處理,分析不同S蛋白表現。(
B)藉由西方墨點法,分析在用mRNA-LNP轉染之後48小時的HEK293T細胞中之S蛋白表現。用抗S及抗GAPDH單株抗體探測濾膜。
圖22A至圖22C.來自特定醣位點缺陷之S mRNA疫苗的免疫反應表徵。自經免疫接種小鼠分離之脾細胞與RBD (A)及S2 (B)肽池一起培育之後,藉由Elispot量測分泌GrzB之細胞。(C)分離出來自經免疫接種小鼠之CD4
+T細胞且與骨髓衍生之DC及全長WT S肽池一起培育,以藉由流式細胞量測術量測分泌IFNγ之T細胞。(A-C)五次獨立實驗之平均值±SD。*P<0.001。
圖23.含有胍基團之傳播子
P1及多價呈現傳播子
P2藉由在胍鎓與mRNA中磷酸根之間形成強鹽橋來促進mRNA與聚合物之黏著。
圖24.引發劑(I0)、傳播子(P1、P2、Pb、P3、Pz)及聚合物反應過程之經設計結構。
圖25A及圖25B. (A)在N/P比率=10下,具有GFP mRNA之共聚物的瓊脂糖凝膠電泳分析。(B)藉由TEM成像之mRNA複合物的粒度。
圖26A至圖26C.在HEK293T細胞中經聚(二硫化物)轉染之GFP mRNA之GFP表現的螢光影像。(A)以N/P比率=10與P1、P3、P1/P3及PEI複合之GFP mRNA;(B)以N/P比率=10與P1/P3、P2/P3、P1/Pb及P2/Pb P1/Pz複合之GFP mRNA;(C)以不同N/P比率複合之GFP mRNA。
圖27.刺突蛋白mRNA-聚合物複合物在不同N/P比率下之瓊脂糖凝膠電泳分析。
圖28. HEK293T細胞中藉由刺突蛋白mRNA-聚合物複合物介導之刺突蛋白表現之化學發光成像。
圖29.在處理不同量比率之聚Gu/刺突蛋白mRNA複合物之後,HEK293T細胞之細胞存活率分析。該比率在0.01至1間變化。誤差條表示標準誤差(平均值±S.D.,n=3)。
<![CDATA[<110> 中央研究院(ACADEMIA SINICA)]]> <![CDATA[<120> 對抗廣譜冠狀病毒變種的信使RNA疫苗 ]]> <![CDATA[<130> A21893/PC0157]]> <![CDATA[<150> US 63/173,752]]> <![CDATA[<151> 2021-04-12]]> <![CDATA[<150> US 63/264,737]]> <![CDATA[<151> 2021-12-01]]> <![CDATA[<160> 52 ]]> <![CDATA[<170> PatentIn version 3.5]]> <![CDATA[<210> 1]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> SARS-CoV-2 (武漢病毒株)]]> <![CDATA[<400> 1]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 2]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 (武漢病毒株)]]> <![CDATA[<400> 2]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 3]]> <![CDATA[<211> ]]> 3822 <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD)]]> <![CDATA[<400> 3]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 4]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> ]]> S-(deg-RBD) <![CDATA[<400> 4]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 5]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-S2)]]> <![CDATA[<400> 5]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctcagaat agcatcgcca tcccaaccca gttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaagc agttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc ccagggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtgc agaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gcaacacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatccaag cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctgc aggagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 6]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-S2)]]> <![CDATA[<400> 6]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 7]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(S2-1194)]]> <![CDATA[<400> 7]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctcagaat agcatcgcca tcccaaccca gttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaagc agttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc ccagggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtgc agaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gcaacacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatccaag cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 8]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(S2-1194)]]> <![CDATA[<400> 8]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 9]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-801)]]> <![CDATA[<400> 9]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 10]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-801)]]> <![CDATA[<400> 10]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 11]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-1194)]]> <![CDATA[<400> 11]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctgc aggagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 12]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-1194)]]> <![CDATA[<400> 12]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 13]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-122-165-234)]]> <![CDATA[<400> 13]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aaccaagcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca accagtgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatcc agatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacaaggt ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 14]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> S-(deg-RBD-122-165-234)]]> <![CDATA[<400> 1]]>4 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Gln Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Gln Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Gln Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 15]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> SARS-CoV-2 (δ病毒株)]]> <![CDATA[<400> 15]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 accgagtcta tcgtgcgctt tcctaatatc acaaacctgt gcccatttgg cgaggtgttc 1020 aacgcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctaa caatagcatc gccatcccaa ccaacttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttcaatttt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggaca aggtggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagaacttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtccaacgg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgaacaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagaatca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc aatgcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgaacgaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 16]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 (δ病毒株)]]> <![CDATA[<400> 16]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 17]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> SARS-CoV-2 (武漢病毒株S-2P病毒株)]]> <![CDATA[<400> 17]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 18]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 ]]>(武漢病毒株S-2P病毒株) <![CDATA[<400> 18]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 19]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> SARS-CoV-2 (δS-2P病毒株)]]> <![CDATA[<400> 19]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 accgagtcta tcgtgcgctt tcctaatatc acaaacctgt gcccatttgg cgaggtgttc 1020 aacgcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctaa caatagcatc gccatcccaa ccaacttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttcaatttt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggacc cgccggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagaacttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtccaacgg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgaacaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagaatca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc aatgcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgaacgaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 20]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> SARS-CoV-2 (δS-2P病毒株)]]> <![CDATA[<400> 20]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 21]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δ病毒株之S-(deg-RBD)]]> <![CDATA[<400> 21]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 gccgaggcga tcgtgcgctt tcctgaaatc acaaacctgt gcccatttgg cgaggtgttc 1020 gaggcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctaa caatagcatc gccatcccaa ccaacttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttcaatttt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggaca aggtggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagaacttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtccaacgg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgaacaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagaatca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc aatgcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgaacgaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 22]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δ病毒株之S-(deg-RBD)]]> <![CDATA[<400> 22]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 23]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD)]]> <![CDATA[<400> 23]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 24]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD)的蛋白質序列]]> <![CDATA[<400> 24]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 25]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δS-2P病毒株之S-(deg-RBD)]]> <![CDATA[<400> 25]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 gccgaggcga tcgtgcgctt tcctgaaatc acaaacctgt gcccatttgg cgaggtgttc 1020 gaggcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctaa caatagcatc gccatcccaa ccaacttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttcaatttt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggacc cgccggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagaacttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtccaacgg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgaacaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagaatca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc aatgcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgaacgaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 26]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δS-2P病毒株之S-(deg-RBD)]]> <![CDATA[<400> 26]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 27]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δ病毒株之S-(deg-S2)]]> <![CDATA[<400> 27]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 accgagtcta tcgtgcgctt tcctaatatc acaaacctgt gcccatttgg cgaggtgttc 1020 aacgcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctca gaatagcatc gccatcccaa cccagttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttccaattt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggaca aggtggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagcagttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtcccaggg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgcagaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagcaaca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc caagcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgcaggaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 28]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δ病毒株之S-(deg-S2)]]> <![CDATA[<400> 28]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Gln Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 29]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P之S-(deg-S2)]]> <![CDATA[<400> 29]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctcagaat agcatcgcca tcccaaccca gttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaagc agttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc ccagggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtgc agaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gcaacacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatccaag cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctgc aggagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 30]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P之S-(deg-S2)]]> <![CDATA[<400> 30]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 31]]> <![CDATA[<211> 3816]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δS-2P病毒株之S-(deg-S2)]]> <![CDATA[<400> 31]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgcgaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctatcgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctggacgtgt actatcacaa gaacaataag agctggatgg agtccggagt gtattctagc 480 gccaacaact gcacatttga gtacgtgagc cagcctttcc tgatggacct ggagggcaag 540 cagggcaatt tcaagaacct gagggagttc gtgtttaaga atatcgacgg ctacttcaaa 600 atctactcta agcacacccc catcaacctg gtgcgcgacc tgcctcaggg cttcagcgcc 660 ctggagcccc tggtggatct gcctatcggc atcaacatca cccggtttca gacactgctg 720 gccctgcaca gaagctacct gacacccggc gactcctcta gcggatggac cgccggcgct 780 gccgcctact atgtgggcta cctccagccc cggaccttcc tgctgaagta caacgagaat 840 ggcaccatca cagacgcagt ggattgcgcc ctggaccccc tgagcgagac aaagtgtaca 900 ctgaagtcct ttaccgtgga gaagggcatc tatcagacat ccaatttcag ggtgcagcca 960 accgagtcta tcgtgcgctt tcctaatatc acaaacctgt gcccatttgg cgaggtgttc 1020 aacgcaaccc gcttcgccag cgtgtacgcc tggaatagga agcggatcag caactgcgtg 1080 gccgactata gcgtgctgta caactccgcc tctttcagca cctttaagtg ctatggcgtg 1140 tcccccacaa agctgaatga cctgtgcttt accaacgtct acgccgattc tttcgtgatc 1200 aggggcgacg aggtgcgcca gatcgccccc ggccagacag gcaagatcgc agactacaat 1260 tataagctgc cagacgattt caccggctgc gtgatcgcct ggaacagcaa caatctggat 1320 tccaaagtgg gcggcaacta caattatcgg taccggctgt ttagaaagag caatctgaag 1380 cccttcgaga gggacatctc tacagaaatc taccaggccg gcagcaagcc ttgcaatggc 1440 gtggagggct ttaactgtta tttcccactc cagtcctacg gcttccagcc cacaaacggc 1500 gtgggctatc agccttaccg cgtggtggtg ctgagctttg agctgctgca cgccccagca 1560 acagtgtgcg gccccaagaa gtccaccaat ctggtgaaga acaagtgcgt gaacttcaac 1620 ttcaacggcc tgaccggcac aggcgtgctg accgagtcca acaagaagtt cctgccattt 1680 cagcagttcg gcagggacat cgcagatacc acagacgccg tgcgcgaccc acagaccctg 1740 gagatcctgg acatcacacc ctgctctttc ggcggcgtga gcgtgatcac acccggcacc 1800 aatacaagca accaggtggc cgtgctgtat cagggcgtga attgtaccga ggtgcccgtg 1860 gctatccacg ccgatcagct gaccccaaca tggcgggtgt acagcaccgg ctccaacgtc 1920 ttccagacaa gagccggatg cctgatcgga gcagagcacg tgaacaattc ctatgagtgc 1980 gacatcccaa tcggcgccgg catctgtgcc tcttaccaga cccagacaaa ctctcgcaga 2040 agagcccgga gcgtggcctc ccagtctatc atcgcctata ccatgtccct gggcgccgag 2100 aacagcgtgg cctactctca gaatagcatc gccatcccaa cccagttcac aatctctgtg 2160 accacagaga tcctgcccgt gtccatgacc aagacatctg tggactgcac aatgtatatc 2220 tgtggcgatt ctaccgagtg cagcaacctg ctgctccagt acggcagctt ttgtacccag 2280 ctgaatagag ccctgacagg catcgccgtg gagcaggata agaacacaca ggaggtgttc 2340 gcccaggtga agcaaatcta caagaccccc cctatcaagg actttggcgg cttccaattt 2400 tcccagatcc tgcctgatcc atccaagcct tctaagcgga gctttatcga ggacctgctg 2460 ttcaacaagg tgaccctggc cgatgccggc ttcatcaagc agtatggcga ttgcctgggc 2520 gacatcgcag ccagggacct gatctgcgcc cagaagttta atggcctgac cgtgctgcca 2580 cccctgctga cagatgagat gatcgcacag tacacaagcg ccctgctggc cggcaccatc 2640 acatccggat ggaccttcgg cgcaggagcc gccctccaga tcccctttgc catgcagatg 2700 gcctataggt tcaacggcat cggcgtgacc cagaatgtgc tgtacgagaa ccagaagctg 2760 atcgccaatc agtttaactc cgccatcggc aagatccagg acagcctgtc ctctacagcc 2820 agcgccctgg gcaagctcca gaatgtggtg aatcagaacg cccaggccct gaataccctg 2880 gtgaagcagc tgagcagcaa cttcggcgcc atctctagcg tgctgaatga catcctgagc 2940 cggctggacc gccgggaggc agaggtgcag atcgaccggc tgatcaccgg ccggctccag 3000 agcctccaga cctatgtgac acagcagctg atcagggccg ccgagatcag ggccagcgcc 3060 aatctggcag caaccaagat gtccgagtgc gtgctgggcc agtctaagag agtggacttt 3120 tgtggcaagg gctatcacct gatgtccttc cctcagtctg ccccacacgg cgtggtgttt 3180 ctgcacgtga cctacgtgcc cgcccaggag aagcagttca ccacagcccc tgccatctgc 3240 cacgatggca aggcccactt tccaagggag ggcgtgttcg tgtcccaggg cacccactgg 3300 tttgtgacac agcgcaattt ctacgagccc cagatcatca ccacagacaa caccttcgtg 3360 agcggcaact gtgacgtggt catcggcatc gtgcagaata ccgtgtatga tccactccag 3420 cccgagctgg acagctttaa ggaggagctg gataagtatt tcaagcaaca cacctcccct 3480 gacgtggatc tgggcgacat cagcggcatc caagcctccg tggtgaacat ccagaaggag 3540 atcgaccgcc tgaacgaggt ggctaagaat ctgcaggaga gcctgatcga cctccaggag 3600 ctgggcaagt atgagcagta catcaagtgg ccctggtaca tctggctggg cttcatcgcc 3660 ggcctgatcg ccatcgtgat ggtgaccatc atgctgtgct gtatgacatc ctgctgttct 3720 tgcctgaagg gctgctgtag ctgtggctcc tgctgtaagt ttgacgagga tgactctgaa 3780 cctgtgctga agggcgtgaa gctgcattac acctaa 3816 <![CDATA[<210> 32]]> <![CDATA[<211> 1271]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> δS-2P病毒株之S-(deg-S2)]]> <![CDATA[<400> 32]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Asp Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser 145 150 155 160 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 165 170 175 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 180 185 190 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 195 200 205 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 210 215 220 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 225 230 235 240 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 245 250 255 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 260 265 270 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 275 280 285 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 290 295 300 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 305 310 315 320 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 325 330 335 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 340 345 350 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 355 360 365 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 370 375 380 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 385 390 395 400 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 405 410 415 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 420 425 430 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 435 440 445 Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 450 455 460 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly 465 470 475 480 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 485 490 495 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 500 505 510 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 515 520 525 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 530 535 540 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 545 550 555 560 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 565 570 575 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 580 585 590 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 595 600 605 Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 610 615 620 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 625 630 635 640 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 645 650 655 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 660 665 670 Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln 675 680 685 Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala 690 695 700 Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile Ser Val 705 710 715 720 Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys 725 730 735 Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu 740 745 750 Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile 755 760 765 Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys 770 775 780 Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Gln Phe 785 790 795 800 Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile 805 810 815 Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile 820 825 830 Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile 835 840 845 Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr 850 855 860 Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile 865 870 875 880 Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe 885 890 895 Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn 900 905 910 Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala 915 920 925 Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly 930 935 940 Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu 945 950 955 960 Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn 965 970 975 Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp 980 985 990 Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln 995 1000 1005 Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala 1010 1015 1020 Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 1025 1030 1035 Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser 1040 1045 1050 Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala 1055 1060 1065 Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 1070 1075 1080 Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln Gly Thr 1085 1090 1095 His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile 1100 1105 1110 Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile 1115 1120 1125 Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu 1130 1135 1140 Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln His Thr 1145 1150 1155 Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln Ala Ser 1160 1165 1170 Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1175 1180 1185 Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys 1190 1195 1200 Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe 1205 1210 1215 Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys 1220 1225 1230 Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys 1235 1240 1245 Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu 1250 1255 1260 Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 33]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(S2-1194)]]> <![CDATA[<400> 33]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccaaccg agtctatcgt gcgctttcct aatatcacaa acctgtgccc atttggcgag 1020 gtgttcaacg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctcagaat agcatcgcca tcccaaccca gttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaagc agttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc ccagggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtgc agaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gcaacacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatccaag cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 34]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(S2-1194)]]> <![CDATA[<400> 3]]>4 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Gln Asn Ser Ile Ala Ile Pro Thr Gln Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Gln Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Gln 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Gln Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Gln 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Gln 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 35]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-801)]]> <![CDATA[<400> 35]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 caattttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 36]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-801)]]> <![CDATA[<400> 36]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Gln Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 37]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-1194)]]> <![CDATA[<400> 37]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aacaatgcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca acaactgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatca acatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctgc aggagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 38]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-1194)]]> <![CDATA[<400> 38]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Gln Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 39]]> <![CDATA[<211> 3822]]> <![CDATA[<212> DNA]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-122-165-234)]]> <![CDATA[<400> 39]]> atgttcgtct tcctggtcct gctgcctctg gtctcctcac agtgcgtcaa tctgacaact 60 cggactcagc tgccacctgc ttatactaat agcttcacca gaggcgtgta ctatcctgac 120 aaggtgttta gaagctccgt gctgcactct acacaggatc tgtttctgcc attctttagc 180 aacgtgacct ggttccacgc catccacgtg agcggcacca atggcacaaa gcggttcgac 240 aatcccgtgc tgccttttaa cgatggcgtg tacttcgcct ctaccgagaa gagcaacatc 300 atcagaggct ggatctttgg caccacactg gactccaaga cacagtctct gctgatcgtg 360 aaccaagcca ccaacgtggt catcaaggtg tgcgagttcc agttttgtaa tgatcccttc 420 ctgggcgtgt actatcacaa gaacaataag agctggatgg agtccgagtt tagagtgtat 480 tctagcgcca accagtgcac atttgagtac gtgagccagc ctttcctgat ggacctggag 540 ggcaagcagg gcaatttcaa gaacctgagg gagttcgtgt ttaagaatat cgacggctac 600 ttcaaaatct actctaagca cacccccatc aacctggtgc gcgacctgcc tcagggcttc 660 agcgccctgg agcccctggt ggatctgcct atcggcatcc agatcacccg gtttcagaca 720 ctgctggccc tgcacagaag ctacctgaca cccggcgact cctctagcgg atggaccgcc 780 ggcgctgccg cctactatgt gggctacctc cagccccgga ccttcctgct gaagtacaac 840 gagaatggca ccatcacaga cgcagtggat tgcgccctgg accccctgag cgagacaaag 900 tgtacactga agtcctttac cgtggagaag ggcatctatc agacatccaa tttcagggtg 960 cagccagccg aggcgatcgt gcgctttcct gaaatcacaa acctgtgccc atttggcgag 1020 gtgttcgagg caacccgctt cgccagcgtg tacgcctgga ataggaagcg gatcagcaac 1080 tgcgtggccg actatagcgt gctgtacaac tccgcctctt tcagcacctt taagtgctat 1140 ggcgtgtccc ccacaaagct gaatgacctg tgctttacca acgtctacgc cgattctttc 1200 gtgatcaggg gcgacgaggt gcgccagatc gcccccggcc agacaggcaa gatcgcagac 1260 tacaattata agctgccaga cgatttcacc ggctgcgtga tcgcctggaa cagcaacaat 1320 ctggattcca aagtgggcgg caactacaat tatctgtacc ggctgtttag aaagagcaat 1380 ctgaagccct tcgagaggga catctctaca gaaatctacc aggccggcag caccccttgc 1440 aatggcgtgg agggctttaa ctgttatttc ccactccagt cctacggctt ccagcccaca 1500 aacggcgtgg gctatcagcc ttaccgcgtg gtggtgctga gctttgagct gctgcacgcc 1560 ccagcaacag tgtgcggccc caagaagtcc accaatctgg tgaagaacaa gtgcgtgaac 1620 ttcaacttca acggcctgac cggcacaggc gtgctgaccg agtccaacaa gaagttcctg 1680 ccatttcagc agttcggcag ggacatcgca gataccacag acgccgtgcg cgacccacag 1740 accctggaga tcctggacat cacaccctgc tctttcggcg gcgtgagcgt gatcacaccc 1800 ggcaccaata caagcaacca ggtggccgtg ctgtatcagg acgtgaattg taccgaggtg 1860 cccgtggcta tccacgccga tcagctgacc ccaacatggc gggtgtacag caccggctcc 1920 aacgtcttcc agacaagagc cggatgcctg atcggagcag agcacgtgaa caattcctat 1980 gagtgcgaca tcccaatcgg cgccggcatc tgtgcctctt accagaccca gacaaactct 2040 cccagaagag cccggagcgt ggcctcccag tctatcatcg cctataccat gtccctgggc 2100 gccgagaaca gcgtggccta ctctaacaat agcatcgcca tcccaaccaa cttcacaatc 2160 tctgtgacca cagagatcct gcccgtgtcc atgaccaaga catctgtgga ctgcacaatg 2220 tatatctgtg gcgattctac cgagtgcagc aacctgctgc tccagtacgg cagcttttgt 2280 acccagctga atagagccct gacaggcatc gccgtggagc aggataagaa cacacaggag 2340 gtgttcgccc aggtgaagca aatctacaag acccccccta tcaaggactt tggcggcttc 2400 aatttttccc agatcctgcc tgatccatcc aagccttcta agcggagctt tatcgaggac 2460 ctgctgttca acaaggtgac cctggccgat gccggcttca tcaagcagta tggcgattgc 2520 ctgggcgaca tcgcagccag ggacctgatc tgcgcccaga agtttaatgg cctgaccgtg 2580 ctgccacccc tgctgacaga tgagatgatc gcacagtaca caagcgccct gctggccggc 2640 accatcacat ccggatggac cttcggcgca ggagccgccc tccagatccc ctttgccatg 2700 cagatggcct ataggttcaa cggcatcggc gtgacccaga atgtgctgta cgagaaccag 2760 aagctgatcg ccaatcagtt taactccgcc atcggcaaga tccaggacag cctgtcctct 2820 acagccagcg ccctgggcaa gctccaggat gtggtgaatc agaacgccca ggccctgaat 2880 accctggtga agcagctgag cagcaacttc ggcgccatct ctagcgtgct gaatgacatc 2940 ctgagccggc tggacccgcc ggaggcagag gtgcagatcg accggctgat caccggccgg 3000 ctccagagcc tccagaccta tgtgacacag cagctgatca gggccgccga gatcagggcc 3060 agcgccaatc tggcagcaac caagatgtcc gagtgcgtgc tgggccagtc taagagagtg 3120 gacttttgtg gcaagggcta tcacctgatg tccttccctc agtctgcccc acacggcgtg 3180 gtgtttctgc acgtgaccta cgtgcccgcc caggagaaga acttcaccac agcccctgcc 3240 atctgccacg atggcaaggc ccactttcca agggagggcg tgttcgtgtc caacggcacc 3300 cactggtttg tgacacagcg caatttctac gagccccaga tcatcaccac agacaacacc 3360 ttcgtgagcg gcaactgtga cgtggtcatc ggcatcgtga acaataccgt gtatgatcca 3420 ctccagcccg agctggacag ctttaaggag gagctggata agtatttcaa gaatcacacc 3480 tcccctgacg tggatctggg cgacatcagc ggcatcaatg cctccgtggt gaacatccag 3540 aaggagatcg accgcctgaa cgaggtggct aagaatctga acgagagcct gatcgacctc 3600 caggagctgg gcaagtatga gcagtacatc aagtggccct ggtacatctg gctgggcttc 3660 atcgccggcc tgatcgccat cgtgatggtg accatcatgc tgtgctgtat gacatcctgc 3720 tgttcttgcc tgaagggctg ctgtagctgt ggctcctgct gtaagtttga cgaggatgac 3780 tctgaacctg tgctgaaggg cgtgaagctg cattacacct aa 3822 <![CDATA[<210> 40]]> <![CDATA[<211> 1273]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 武漢S-2P病毒株之S-(deg-RBD-122-165-234)]]> <![CDATA[<400> 40]]> Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Gln Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Gln Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Gln Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Ala Glu Ala Ile Val Arg Phe Pro Gln Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Gln Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 885 890 895 Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu 1205 1210 1215 Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met 1220 1225 1230 Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 1235 1240 1245 Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro 1250 1255 1260 Val Leu Lys Gly Val Lys Leu His Tyr Thr 1265 1270 <![CDATA[<210> 41]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 41]]> Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 1 5 10 <![CDATA[<210> 42]]> <![CDATA[<211> 16]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 42]]> Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 1 5 10 15 <![CDATA[<210> 43]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 43]]> Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 1 5 10 <![CDATA[<210> 44]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> ]]> 人工序列 <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 44]]> Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 1 5 10 <![CDATA[<210> 45]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 45]]> Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr 1 5 10 <![CDATA[<210> 46]]> <![CDATA[<211> 15]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 46]]> Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly 1 5 10 15 <![CDATA[<210> 47]]> <![CDATA[<211> 13]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 47]]> Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys 1 5 10 <![CDATA[<210> 48]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<22]]>0>]]> <br/><![CDATA[<223> 免疫原性肽]]> <br/> <br/><![CDATA[<400> 48]]> <br/> <br/><![CDATA[Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr 1 5 10 <![CDATA[<210> 49]]> <![CDATA[<211> 19]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 49]]> Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1 5 10 15 His Thr Ser <![CDATA[<210> 50]]> <![CDATA[<211> 14]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 50]]> Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala 1 5 10 <![CDATA[<210> 51]]> <![CDATA[<211> 10]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 51]]> Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1 5 10 <![CDATA[<210> 52]]> <![CDATA[<211> 11]]> <![CDATA[<212> PRT]]> <![CDATA[<213> 人工序列]]> <![CDATA[<220>]]> <![CDATA[<223> 免疫原性肽]]> <![CDATA[<400> 52]]> Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 1 5 10
Claims (49)
- 一種經修飾核酸分子,其編碼經修飾刺突蛋白,該經修飾刺突蛋白包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處天冬醯胺(N)成為麩醯胺酸(Q)之胺基酸取代,其中X為除脯胺酸外之任何胺基酸殘基,且S/T表示絲胺酸或蘇胺酸殘基。
- 如請求項1之經修飾核酸分子,其包含一或多個在N鍵聯醣基化序列子(N-X-S/T)處之胺基酸缺失或添加,以消除N鍵聯聚醣序列子。
- 如請求項1之經修飾核酸分子,其包含一或多個在O鍵聯醣基化位點處S/T成為丙胺酸(A)之胺基酸取代,以消除O鍵聯醣基化位點。
- 一種經修飾核酸分子,其為mRNA,或雙股或單股DNA。
- 如請求項1至4中任一項之經修飾核酸分子,其中該經修飾刺突蛋白衍生自SARS-CoV-2刺突蛋白。
- 如請求項1至4中任一項之經修飾核酸分子,其中該刺突蛋白包含SEQ ID NO: 2、16、18或20之胺基酸序列,或與SEQ ID NO: 2、16、18或20之胺基酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的胺基酸序列。
- 如請求項6之經修飾核酸分子,其中編碼SEQ ID NO: 2、16、18或20之胺基酸序列的該核酸分子為分別包含SEQ ID NO: 1、15、17或19之核苷酸序列的mRNA,或分別包含與SEQ ID NO: 1、15、17或19之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列的mRNA。
- 如請求項1至4中任一項之經修飾核酸分子,其中本文所描述之該經修飾刺突蛋白包含SEQ ID NO: 4、22、24或26之胺基酸序列,其中該經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD)。
- 如請求項8之經修飾核酸分子,其中編碼SEQ ID NO: 4、22、24或26之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 3、21、23或25之核苷酸序列,或分別包含與SEQ ID NO: 3、21、23或25之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中本文所描述之該經修飾刺突蛋白包含SEQ ID NO: 6、28、30或32之胺基酸序列,其中該經修飾刺突蛋白包含缺少醣基化位點之S2次單元。
- 如請求項10之經修飾核酸分子,其中編碼SEQ ID NO: 6、28、30或32之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 5、27、29或31之核苷酸序列,或分別包含與SEQ ID NO: 5、27、29或31之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中本文所描述之該經修飾刺突蛋白包含SEQ ID NO: 8或34之胺基酸序列,其中該經修飾刺突蛋白包含由單個醣基化位點組成之S2次單元。在一些實施例中,該單個醣基化位點係在位置N1194處。
- 如請求項12之經修飾核酸分子,其中編碼SEQ ID NO: 8或34之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 7或33之核苷酸序列,或分別包含與SEQ ID NO: 7或33之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中該經修飾刺突蛋白包含SEQ ID NO: 10或36之胺基酸序列,其中該經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD),及N801成為Q801之胺基酸取代。
- 如請求項14之經修飾核酸分子,其中編碼SEQ ID NO: 10或36之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 9或35之核苷酸序列,或分別包含與SEQ ID NO: 9或35之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中本文所描述之該經修飾刺突蛋白包含SEQ ID NO: 12或38之胺基酸序列,其中該經修飾刺突蛋白包含缺少醣基化位點之受體結合域(RBD),及N1194成為Q1194之胺基酸取代。
- 如請求項16之經修飾核酸分子,其中編碼SEQ ID NO: 12或38之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 11或37之核苷酸序列,或分別包含與SEQ ID NO: 11或37之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中本文所描述之該經修飾刺突蛋白包含SEQ ID NO: 14或40之胺基酸序列,其中該經修飾刺突蛋白包含缺少醣基化位點之經修飾受體結合域(RBD),及N122成為Q122、N165成為Q165及N234成為Q234之胺基酸取代。
- 如請求項18之經修飾核酸分子,其中編碼SEQ ID NO: 14或40之胺基酸序列的該經修飾核酸分子分別包含SEQ ID NO: 13或39之核苷酸序列,或分別包含與SEQ ID NO: 13或39之核苷酸序列具有至少約99%、98%、97%、96%、95%、90%、85%或80%一致性的核苷酸序列。
- 如請求項1至4中任一項之經修飾核酸分子,其中該經修飾刺突蛋白包含缺少醣基化位點之S1次單元。
- 如請求項1至4中任一項之經修飾核酸分子,其中該經修飾刺突蛋白包含缺少醣基化位點之S1及S2次單元兩者。
- 如請求項1至4中任一項之經修飾核酸分子,其中S-(deg-RBD)之mRNA具有SEQ ID NO: 3、21、23或25之序列,S-(deg-S2)之mRNA或DNA具有SEQ ID NO: 5、27、29或31之序列,S-(deg-S2-1194)之mRNA或DNA具有SEQ ID NO: 7或33之序列,S-(deg-RBD-801)之mRNA或DNA具有SEQ ID NO: 9或35之序列,S-(deg-RBD-1194)之mRNA或DNA具有SEQ ID NO: 11或37之序列,S-(deg-RBD-122-165-234)之mRNA或DNA具有SEQ ID NO: 13或39之序列。
- 如請求項1至22中任一項之經修飾核酸分子,其可用作冠狀病毒mRNA疫苗。
- 如請求項1至23中任一項之經修飾核酸分子,其中該經修飾核酸分子之免疫接種引起BiP/GRP78、XBP1及p-eIF2α之上調,以誘發細胞凋亡及CD8 T細胞反應。
- 如請求項1至23中任一項之經修飾核酸分子,其中該冠狀病毒(CoV)係選自由以下組成之群:α-CoV、β-CoV、γ-CoV、δ-CoV2及ο-CoV2。
- 一種組合疫苗,其包含如請求項23之mRNA疫苗及一或多種額外疫苗。
- 如請求項26之組合疫苗,其中該額外疫苗係選自一或多種COVID-19疫苗、流行性感冒(流感)疫苗、腺病毒疫苗、炭疽疫苗、霍亂疫苗、白喉疫苗、A或B型肝炎疫苗、HPV疫苗、麻疹疫苗、流行性腮腺炎疫苗、天花疫苗、輪狀病毒疫苗、肺結核疫苗、肺炎鏈球菌疫苗及b型流感嗜血桿菌(Haemophilus influenzae)疫苗及其任何組合。
- 一種奈米粒子,其基於胍且用作載劑,以將如請求項1至25中任一項之經修飾核酸分子遞送至個體。
- 如請求項28之奈米粒子,其為脂質體或聚合物囊泡。
- 一種mRNA奈米簇,其包含調配於脂質奈米粒子中的如請求項26或27之疫苗。
- 如請求項30之mRNA奈米簇,其中該脂質奈米粒子為可生物降解之脂質奈米粒子。
- 如請求項30或31之mRNA奈米簇,其中該脂質奈米粒子為基於胍之聚合物。
- 一種mRNA奈米簇,其包含囊封有mRNA疫苗之脂質奈米粒子,其中可生物降解之脂質奈米粒子包含基於胍及兩性離子之單元,其中基於胍及兩性離子之基團連接至脂質尾,且其中該等基於胍之基團黏附於mRNA,由此在胍鎓基團與該mRNA中之磷酸根之間形成鹽橋。
- 如請求項28或29之奈米粒子或如請求項30至34中任一項之mRNA奈米簇,其中該基於胍之聚合物形成共聚物,諸如P1/P3共聚物、P2/P3共聚物、P1/Pb共聚物、P2/Pb共聚物、P1/Pz共聚物及P2/Pz共聚物。
- 如請求項28或29之奈米粒子或如請求項30至36中任一項之mRNA奈米簇,其具有約1至約100之奈米粒子/mRNA (N/P)比率。
- 如請求項28或29之奈米粒子或如請求項30至37中任一項之mRNA奈米簇,其具有約10或約20之奈米粒子/mRNA (N/P)比率。
- 一種奈米粒子組合物,其包含奈米粒子連接於如請求項23之mRNA疫苗。
- 一種預防或治療冠狀病毒感染之方法,其包含向已感染冠狀病毒或處於感染冠狀病毒之風險下的個體投與有效量的如請求項1至25中任一項之經修飾核酸分子、如請求項28或29之奈米粒子、如請求項30至38中任一項之mRNA奈米簇或如請求項39之奈米粒子組合物。
- 一種增強適應性免疫反應之方法,其包含向個體投與有效量的如請求項1至25中任一項之經修飾核酸分子、如請求項28或29之奈米粒子、如請求項30至38中任一項之mRNA奈米簇或如請求項39之奈米粒子組合物。
- 如請求項41或42之方法,其中如請求項1至25中任一項之經修飾核酸分子、如請求項28或29之奈米粒子、如請求項30至38中任一項之mRNA奈米簇或如請求項39之奈米粒子組合物係投與初始劑量,及兩次、三次或四次加強劑量。
- 如請求項41或42之方法,其中如請求項1至25中任一項之經修飾核酸分子、如請求項28或29之奈米粒子、如請求項30至38中任一項之mRNA奈米簇或如請求項39之奈米粒子組合物係投與初始劑量,且在該初始劑量之後約一個月、約兩個月、約三個月、約四個月、約五個月或約六個月投與至少一次加強劑量。
- 如請求項41或42之方法,其中該劑量範圍介於5 μg至50 μg之如請求項1至25中任一項之經修飾核酸分子。
- 如請求項41或42之方法,其中該劑量為30 μg。
- 如請求項41或42之方法,其中如請求項1至25中任一項之經修飾核酸分子、如請求項28或29之奈米粒子、如請求項30至38中任一項之mRNA奈米簇或如請求項39之奈米粒子組合物係經由靜脈內途徑、肌肉內途徑、皮內途徑或皮下途徑投與,或藉由輸注或鼻用噴霧投與。
- 一種免疫原性肽,其包含至少一個選自由以下組成之群的胺基酸序列:TESIVRFPNITNL (SEQ ID NO: 41)、NITNLCPFGEVFNATR (SEQ ID NO: 42)、LYNSASFSTFK (SEQ ID NO: 43)、LDSKVGGNYN (SEQ ID NO: 44)、KSNLKPFERDIST (SEQ ID NO: 45)、KPFERDISTEIYQAG (SEQ ID NO: 46)、GPKKSTNLVKNKC (SEQ ID NO: 47)、NCDVVIGIVNNTVY (SEQ ID NO: 48)、PELDSFKEELDKYFKNHTS (SEQ ID NO: 49)、VNIQKEIDRLNEVA (SEQ ID NO: 50)、NLNESLIDLQ (SEQ ID NO: 51)及LGKYEQYIKWP (SEQ ID NO: 52)或與SEQ ID NO: 41至52中之任一者具有至少約99%、98%、97%、96%、95%或90%一致性的胺基酸序列。
- 如請求項47之免疫原性肽,其包含至少一個選自由SEQ ID NO: 41至43及45至51組成之群的胺基酸序列。
- 一種免疫原性組合物,其包含如請求項47或48之免疫原性肽。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163173752P | 2021-04-12 | 2021-04-12 | |
US63/173,752 | 2021-04-12 | ||
US202163264737P | 2021-12-01 | 2021-12-01 | |
US63/264,737 | 2021-12-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
TW202307212A true TW202307212A (zh) | 2023-02-16 |
Family
ID=83639810
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW111113932A TW202307212A (zh) | 2021-04-12 | 2022-04-12 | 對抗廣譜冠狀病毒變種的信使rna疫苗 |
Country Status (12)
Country | Link |
---|---|
US (1) | US20240066113A1 (zh) |
EP (1) | EP4322996A2 (zh) |
JP (1) | JP2023552265A (zh) |
KR (1) | KR20230124888A (zh) |
AU (1) | AU2022258955A1 (zh) |
BR (1) | BR112023005961A2 (zh) |
CA (1) | CA3197160A1 (zh) |
CO (1) | CO2023004253A2 (zh) |
IL (1) | IL302091A (zh) |
MX (1) | MX2023003762A (zh) |
TW (1) | TW202307212A (zh) |
WO (1) | WO2022221835A2 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021226533A1 (en) | 2020-05-08 | 2021-11-11 | Academia Sinica | Chimeric influenza vaccines |
CA3197160A1 (en) * | 2021-04-12 | 2022-10-20 | Academia Sinica | Messenger rna vaccines against wide spectrum of coronavirus variants |
TW202334429A (zh) | 2021-10-01 | 2023-09-01 | 中央研究院 | Sars-cov-2棘蛋白特異性抗體及其用途 |
TW202333780A (zh) | 2021-11-29 | 2023-09-01 | 德商拜恩技術股份公司 | 冠狀病毒疫苗 |
WO2023147092A2 (en) | 2022-01-28 | 2023-08-03 | BioNTech SE | Coronavirus vaccine |
US11878055B1 (en) | 2022-06-26 | 2024-01-23 | BioNTech SE | Coronavirus vaccine |
WO2024086575A1 (en) | 2022-10-17 | 2024-04-25 | BioNTech SE | Combination vaccines against coronavirus infection, influenza infection, and/or rsv infection |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4007597A2 (en) * | 2019-08-01 | 2022-06-08 | ACM Biolabs Pte Ltd | A method of eliciting an immune response by administering a population of polymersomes having an associated antigen together with a population of polymersomes having an associated adjuvant as well as compositions comprising the two populations of polymersomes |
US10953089B1 (en) * | 2020-01-27 | 2021-03-23 | Novavax, Inc. | Coronavirus vaccine formulations |
CN112626124B (zh) * | 2020-10-15 | 2023-04-11 | 广州达博生物制品有限公司 | 一种病毒保存试剂 |
CA3197160A1 (en) * | 2021-04-12 | 2022-10-20 | Academia Sinica | Messenger rna vaccines against wide spectrum of coronavirus variants |
-
2022
- 2022-04-12 CA CA3197160A patent/CA3197160A1/en active Pending
- 2022-04-12 IL IL302091A patent/IL302091A/en unknown
- 2022-04-12 BR BR112023005961A patent/BR112023005961A2/pt unknown
- 2022-04-12 AU AU2022258955A patent/AU2022258955A1/en active Pending
- 2022-04-12 TW TW111113932A patent/TW202307212A/zh unknown
- 2022-04-12 EP EP22789117.3A patent/EP4322996A2/en active Pending
- 2022-04-12 JP JP2023520111A patent/JP2023552265A/ja active Pending
- 2022-04-12 US US18/029,758 patent/US20240066113A1/en active Pending
- 2022-04-12 WO PCT/US2022/071679 patent/WO2022221835A2/en active Application Filing
- 2022-04-12 MX MX2023003762A patent/MX2023003762A/es unknown
- 2022-04-12 KR KR1020237014874A patent/KR20230124888A/ko active Search and Examination
-
2023
- 2023-03-31 CO CONC2023/0004253A patent/CO2023004253A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
BR112023005961A2 (pt) | 2023-10-24 |
CA3197160A1 (en) | 2022-10-20 |
MX2023003762A (es) | 2023-06-01 |
AU2022258955A1 (en) | 2023-05-11 |
AU2022258955A9 (en) | 2023-07-13 |
WO2022221835A3 (en) | 2023-03-16 |
US20240066113A1 (en) | 2024-02-29 |
IL302091A (en) | 2023-06-01 |
KR20230124888A (ko) | 2023-08-28 |
CO2023004253A2 (es) | 2023-06-20 |
JP2023552265A (ja) | 2023-12-15 |
EP4322996A2 (en) | 2024-02-21 |
WO2022221835A2 (en) | 2022-10-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW202307212A (zh) | 對抗廣譜冠狀病毒變種的信使rna疫苗 | |
TWI737584B (zh) | 手、足及口疫苗及其製備及使用方法 | |
JP2023526495A (ja) | SARS-CoV-2ワクチン | |
Qayoom et al. | Adverse cutaneous drug reactions-a clinico-demographic study in a tertiary care teaching hospital of the Kashmir Valley, India | |
WO2023086961A1 (en) | Sars-cov-2 spike fused to a hepatitis b surface antigen | |
BR112015023738B1 (pt) | Vacinas de nucleoproteina influenza | |
TW202208400A (zh) | 來自sars–cov–2之保守肽抗原決定基於開發廣泛型covid–19疫苗之用途 | |
KR102439864B1 (ko) | 재조합 바이러스, 이를 포함하는 조성물 및 그 용도 | |
US11253587B2 (en) | Vaccine compositions for the treatment of coronavirus | |
US20220409717A1 (en) | Chikungunya virus-like particle vaccine and methods of using the same | |
WO2012040266A2 (en) | Gene-based adjuvants and compositions thereof to increase antibody production in response to gene-based vaccines | |
CN116940588A (zh) | 对抗广谱冠状病毒变种的信使rna疫苗 | |
EP4144752A1 (en) | Viral-like particles for the treatment or prevention of an infection by a coronaviridae virus | |
US20240092840A1 (en) | Vaccine formulation comprising recombinant overlapping peptides and native proteins | |
CA3221041A1 (en) | Virus-like particle vaccine for coronavirus | |
WO2019069561A1 (ja) | インフルエンザに対する医薬 | |
Huber et al. | Whole-inactivated influenza virus as an adjuvant for influenza peptide antigens | |
Soema et al. | Whole inactvated influenza virus as an adjuvant for influenza peptide antigens |