CN114191552B - 抗新型冠状病毒SARS-CoV-2的药物及其应用 - Google Patents
抗新型冠状病毒SARS-CoV-2的药物及其应用 Download PDFInfo
- Publication number
- CN114191552B CN114191552B CN202111416989.0A CN202111416989A CN114191552B CN 114191552 B CN114191552 B CN 114191552B CN 202111416989 A CN202111416989 A CN 202111416989A CN 114191552 B CN114191552 B CN 114191552B
- Authority
- CN
- China
- Prior art keywords
- cov
- sars
- novel coronavirus
- virus
- hcl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 45
- 229940079593 drug Drugs 0.000 title claims abstract description 27
- 241001678559 COVID-19 virus Species 0.000 title claims abstract description 25
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000010076 replication Effects 0.000 claims description 8
- 239000003443 antiviral agent Substances 0.000 claims description 6
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 claims description 4
- 239000002955 immunomodulating agent Substances 0.000 claims description 4
- 229940121354 immunomodulator Drugs 0.000 claims description 4
- 229960004525 lopinavir Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000003172 expectorant agent Substances 0.000 claims description 3
- 230000002584 immunomodulator Effects 0.000 claims description 3
- -1 mucolytic Substances 0.000 claims description 3
- AEUAEICGCMSYCQ-UHFFFAOYSA-N 4-n-(7-chloroquinolin-1-ium-4-yl)-1-n,1-n-diethylpentane-1,4-diamine;dihydrogen phosphate Chemical compound OP(O)(O)=O.ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 AEUAEICGCMSYCQ-UHFFFAOYSA-N 0.000 claims description 2
- 102000006992 Interferon-alpha Human genes 0.000 claims description 2
- 108010047761 Interferon-alpha Proteins 0.000 claims description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 2
- 239000002221 antipyretic Substances 0.000 claims description 2
- 229940124584 antitussives Drugs 0.000 claims description 2
- 229960002328 chloroquine phosphate Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000133 nasal decongestant Substances 0.000 claims description 2
- 229960000329 ribavirin Drugs 0.000 claims description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 2
- KCFYEAOKVJSACF-UHFFFAOYSA-N umifenovir Chemical compound CN1C2=CC(Br)=C(O)C(CN(C)C)=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 KCFYEAOKVJSACF-UHFFFAOYSA-N 0.000 claims description 2
- 229960004626 umifenovir Drugs 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims 1
- 230000000954 anitussive effect Effects 0.000 claims 1
- 230000001754 anti-pyretic effect Effects 0.000 claims 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims 1
- 230000003419 expectorant effect Effects 0.000 claims 1
- 230000000510 mucolytic effect Effects 0.000 claims 1
- 241000700605 Viruses Species 0.000 abstract description 14
- 150000001875 compounds Chemical class 0.000 abstract description 13
- 241000711573 Coronaviridae Species 0.000 abstract description 10
- 208000025721 COVID-19 Diseases 0.000 abstract description 9
- 208000015181 infectious disease Diseases 0.000 abstract description 9
- 238000012360 testing method Methods 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 206010035664 Pneumonia Diseases 0.000 abstract description 4
- 230000001413 cellular effect Effects 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract description 2
- 230000035755 proliferation Effects 0.000 abstract description 2
- 230000003612 virological effect Effects 0.000 abstract description 2
- 229940126247 SARS-CoV-2 inhibitor Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 13
- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 7
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 7
- 229960000590 celecoxib Drugs 0.000 description 7
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 7
- 229960001346 nilotinib Drugs 0.000 description 7
- 229960004622 raloxifene Drugs 0.000 description 7
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 7
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 7
- WDQPAMHFFCXSNU-BGABXYSRSA-N clofazimine Chemical compound C12=CC=CC=C2N=C2C=C(NC=3C=CC(Cl)=CC=3)C(=N/C(C)C)/C=C2N1C1=CC=C(Cl)C=C1 WDQPAMHFFCXSNU-BGABXYSRSA-N 0.000 description 6
- 229960004287 clofazimine Drugs 0.000 description 6
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 6
- CBPNZQVSJQDFBE-PXVOFZQNSA-N temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-PXVOFZQNSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- NJXWZWXCHBNOOG-UHFFFAOYSA-N 3,3-diphenylpropyl(1-phenylethyl)azanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C(C)[NH2+]CCC(C=1C=CC=CC=1)C1=CC=CC=C1 NJXWZWXCHBNOOG-UHFFFAOYSA-N 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 5
- 229960004005 amlodipine besylate Drugs 0.000 description 5
- BTYHAFSDANBVMJ-UHFFFAOYSA-N conivaptan hydrochloride Chemical compound Cl.C12=CC=CC=C2C=2NC(C)=NC=2CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 BTYHAFSDANBVMJ-UHFFFAOYSA-N 0.000 description 5
- 229960004638 fendiline hcl Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 5
- DWKVCQXJYURSIQ-UHFFFAOYSA-N n-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-1-benzofuran-5-yl]methanesulfonamide;hydron;chloride Chemical compound Cl.C1=CC(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)OC2=CC=C(NS(C)(=O)=O)C=C12 DWKVCQXJYURSIQ-UHFFFAOYSA-N 0.000 description 5
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 description 5
- 238000003753 real-time PCR Methods 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- BXDAOUXDMHXPDI-UHFFFAOYSA-N trifluoperazine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 BXDAOUXDMHXPDI-UHFFFAOYSA-N 0.000 description 5
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 5
- YQNWZWMKLDQSAC-UHFFFAOYSA-N vortioxetine Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 YQNWZWMKLDQSAC-UHFFFAOYSA-N 0.000 description 5
- 229960002263 vortioxetine Drugs 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108010087230 Sincalide Proteins 0.000 description 4
- QBSGXIBYUQJHMJ-UHFFFAOYSA-N bromochlorosalicylanilide Chemical compound OC1=CC=C(Br)C=C1C(=O)NC1=CC=C(Cl)C=C1 QBSGXIBYUQJHMJ-UHFFFAOYSA-N 0.000 description 4
- 238000010609 cell counting kit-8 assay Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 210000003501 vero cell Anatomy 0.000 description 4
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 3
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 3
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 3
- 208000037847 SARS-CoV-2-infection Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 2
- 241000315672 SARS coronavirus Species 0.000 description 2
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 229960001830 amprenavir Drugs 0.000 description 2
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229960001936 indinavir Drugs 0.000 description 2
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
- 229960000884 nelfinavir Drugs 0.000 description 2
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229960000311 ritonavir Drugs 0.000 description 2
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 2
- 229960001852 saquinavir Drugs 0.000 description 2
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229960002073 sertraline Drugs 0.000 description 2
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 2
- 229960002784 thioridazine Drugs 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 208000001528 Coronaviridae Infections Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013500 data storage Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 125000004474 heteroalkylene group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical compound NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- RWWYLEGWBNMMLJ-MEUHYHILSA-N remdesivir Drugs C([C@@H]1[C@H]([C@@H](O)[C@@](C#N)(O1)C=1N2N=CN=C(N)C2=CC=1)O)OP(=O)(N[C@@H](C)C(=O)OCC(CC)CC)OC1=CC=CC=C1 RWWYLEGWBNMMLJ-MEUHYHILSA-N 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 1
- 229950010550 resiquimod Drugs 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明公开了一系列抗新型冠状病毒SARS‑CoV‑2的药物及其应用,体外细胞试验结果表明:所述的化合物能显著抑制SARS‑CoV‑2对正常细胞的侵染,在细胞水平对新型冠状病毒SARS‑CoV‑2有抑制作用,能显著降低病毒在细胞中的毒价,并抑制其在细胞中的增殖,且具有剂量依赖性。因此,可作为新型冠状病毒SARS‑CoV‑2抑制剂,具有治疗人感染该病毒后导致的COVID‑19肺炎,或者动物感染后导致的其它疾病的潜力。
Description
技术领域
本发明属于病毒学领域和药物化学领域,具体是涉及抑制新型冠状病毒SARS-CoV-2 病毒复制的化合物,该化合物抑制SARS-CoV-2病毒复制的机制,以及该化合物在预防和治疗与SARS-CoV-2病毒引起的相关疾病,尤其是与炎症,自身免疫相关疾病上的用途。
背景技术
新型冠状病毒SARS-CoV-2与中东呼吸综合征冠状病毒MERS-CoV,严重急性呼吸综合征冠状病毒SARS-CoV同属于冠状病毒科,冠状病毒(Coronavirus,CoVs)为有包膜的单股正链RNA病毒,其基因组长大约为26000-32000bp,是目前已知的最大的RNA病毒。
目前人们迫切需要有效的抗病毒药物来对抗 SARS-CoV-2的感染,这不仅可以减轻患者的疾病负担,而且可以降低患者感染他人的风险。而开发新型的药物需要数年的时间来确定其安全性和有效性,这对于在短期内控制 SARS-CoV-2的感染来说可能并不实际。因此最快捷的方式是从FDA上市药物中筛选抵抗 SARS-CoV-2感染的药物。目前,已在广泛应用抗病毒药物如:沙奎那韦(saquinavir)、茚地那韦(indinavir)、利托那韦(ritonavir)、奈非那韦(nelfinavir)、安普那韦(amprenavir)和洛匹那韦 (lopinavir)主要用于人类免疫缺乏病毒(HIV),一种导致获得性免疫缺陷综合征(AIDS)及其相关病变的病原性反转录病毒。吉利德科学公司研发的抗埃博拉病毒的试验药物瑞德西韦(remdesivir),可抑制RNA合成酶(RdRp),有希望抑制COVID-19冠状病毒。因此,目前迫切需要找到更多安全、有效的治疗冠状病毒的药物。然而,上述药物具有毒副作用,可能对病人本身造成不必要的损伤,因此寻找一种毒性小的抗SARS-CoV-2药物成为治疗COVID-19急需的解决方案。
发明内容
本发明所要解决的技术问题是,针对上述存在的问题,提供一种避免有严重毒副作用的药物的使用,且具有稳定效果的治疗COVID-19方法。
为解决上述技术问题,本发明的技术方案如下:
一种抗新型冠状病毒SARS-CoV-2的药物组合物,所述药物可以抑制SARS-CoV-2病毒的复制,所述药物包括有效量的Amlodipine Besylate、Fendiline HCl、DronedaroneHCl、 Trifluoperazine 2HCl、Tetrandrine、Conivaptan HCl、Nilotinib、Vandetanib(ZD6474)、Clofazimine、Sertraline HCl、Thioridazine HCl、Celecoxib、Vortioxetine、Monensin sodium salt、Actidione、Raloxifene HCl、Temsirolimus(CCI-779,NSC683864)、Salifungin中的一种或多种。
进一步的,这种药物组合物中的有效成分还可以为上述化合物的缀合物,所述缀合物是为了施用治疗分子或并入标记,其实例包括但不限于烷基、烯基、炔基、酰氨基、氨基、醚、硫醚、酯、亚烷基、杂亚烷基、芳基或杂环基,其各自均可如本领域所公知的任选取代的。
进一步的,本发明提供上述药物组合物在制备治疗或预防新型冠状病毒的药物中的用途,其中所述冠状病毒为新型冠状病毒SARS-CoV-2、MERS-CoV、SARS-CoV。
进一步的,本发明提供一种药物组合物在制备治疗或预防冠状病毒的药物中的用途,所述组合物为Amlodipine Besylate、Fendiline HCl、Dronedarone HCl、Trifluoperazine 2HCl、 Tetrandrine、Conivaptan HCl、Nilotinib、Vandetanib(ZD6474)、Clofazimine、Sertraline HCl、 Thioridazine HCl、Celecoxib、Vortioxetine、Monensin sodium salt、Actidione、Raloxifene HCl、Temsirolimus(CCI-779,NSC683864)、Salifungin中的一种或多种;
进一步的,本发明提供一种药物组合物在制备治疗或预防感染病毒后导致的COVID-19肺炎的药物中的用途,所述组合物为Amlodipine Besylate、Fendiline HCl、Dronedarone HCl、Trifluoperazine 2HCl、Tetrandrine、Conivaptan HCl、Nilotinib、Vandetanib(ZD6474)、Clofazimine、Sertraline HCl、Thioridazine HCl、Celecoxib、Vortioxetine、 Monensin sodium salt、Actidione、Raloxifene HCl、Temsirolimus(CCI-779,NSC 683864)、 Salifungin中的一种或多种。
优选的,所述组合物为Nilotinib、Clofazimine、Celecoxib、Actidione、Raloxifene HCl 中的一种或多种。
优选的,所述组合物中还包括至少一种选自抗病毒剂、皮质类固醇、免疫调节剂、血管活性药物和治疗病毒感染和/或由病毒感染引起的疾病和已知药物的治疗剂,优选的,其中所述的治疗剂是抗病毒剂优选的,其中所述的治疗剂是免疫调节剂;
优选的,治疗剂选自干扰素,咪喹莫特,瑞喹莫德,鬼臼脂素,博来霉素和类视黄醇;
优选的,其中所述的治疗剂选自干扰素-α、洛匹那韦、利诺那韦、利巴韦林、磷酸氯喹、阿比多尔;
优选的,所述组合物中还包括至少一种选自镇咳药,粘液溶解药,祛痰药,退热药,镇痛药和鼻减充血剂;
优选的,所述病毒为新型冠状病毒SARS-CoV-2、MERS-CoV、SARS-CoV。
进一步,本发明提供一种药物组合物在制备治疗或预防感染病毒后导致的COVID-19 肺炎的药物中的用途,其中包括给予有效量的上述药物组合物和/或其药学上可接受的盐,多晶型物,溶剂合物,水合物,代谢物,前药或非对映异构体形式;优选的,包含在药学上可接受的载体。
进一步,上述的药物组合物经口服,胃肠外,静脉内,肌内,透皮,经由口腔途径,皮下或通过栓剂。
发明效果
本发明的积极效果在于在细胞水平内证明了Amlodipine Besylate、FendilineHCl、 Dronedarone HCl、Trifluoperazine 2HCl、Tetrandrine、Conivaptan HCl、Nilotinib、Vandetanib(ZD6474)、Clofazimine、Sertraline HCl、Thioridazine HCl、Celecoxib、Vortioxetine、 Monensin sodium salt、Actidione、Raloxifene HCl、Temsirolimus(CCI-779,NSC 683864)、 Salifungin等18种FDA上市药物可以有效的抑制SARS-CoV-2病毒的复制,这些化合物可以直接成为治疗SARS-CoV-2的药物。
体外细胞试验结果表明:上述18种药物及其组合物对Vero正常细胞的毒性作用很小,但是能显著抑制SARS-CoV-2病毒对正常细胞的侵染,在细胞水平对新型冠状病毒SARS-CoV-2有抑制作用,能显著降低病毒在细胞中的毒价,并抑制其在细胞中的增殖,且具有剂量依赖性。
因此,上述18种药物及其组合物可作为新型冠状病毒SARS-CoV-2的复制抑制剂,具有治疗人感染该病毒后导致的COVID-19肺炎,或者动物感染后导致的其它疾病的潜力,同时还具有安全性高,毒副作用小等优点。
附图说明
图1化合物对Vero细胞中SARS-CoV-2病毒复制的抑制,其中,(a)AmlodipineBesylate、 (b)Fendiline HCl、(c)Dronedarone HCl、(d)Trifluoperazine 2HCl、(e)Tetrandrine、(f)Conivaptan HCl、(g)Nilotinib、(h)Vandetanib(ZD6474)、(i)Clofazimine、(j)Sertraline HCl、 (k)Thioridazine HCl、(l)Celecoxib、(m)Vortioxetine、(n)Monensin sodium salt、(o)Actidione、 (p)Raloxifene HCl、(q)Temsirolimus(CCI-779,NSC 683864)、(r)Salifungin
具体实施方式
非洲绿猴肾细胞Vero购自ATCC;SARS-CoV-2病毒由样本中分离;一步法绝对定量PCR酶Fast Virus 1-Step Master Mix(4444434),Trizol LS购自Thermo;核酸提取试剂盒Direct-zolTMRNA MiniPrep(R2052)购自Zymo Research;CCK8试剂盒(40203)购自上海翊圣生物科技有限公司。
1.上清中RNA提取
按照核酸提取试剂盒说明书操作,具体如下:
1)在加入Trizol LS的样品中加入等体积的无水乙醇,混匀后将液体转移到Zymo-SpinTM IICR柱上,该柱子放置在收集管上,10000g离心1min
2)将Zymo-SpinTM IICR柱转移到新的收集管上
3)在Zymo-SpinTM IICR柱中加入400μl的Direct-zolTM RNA PreWash,10000g离心1min,弃掉流穿液后,重复该步骤
4)在Zymo-SpinTM IICR柱中加入700μl的RNA Wash Buffer,10000g离心2min
5)将Zymo-SpinTM IICR柱转移到干净的EP管上,加入50μl的无核酸酶的水,10000g离心1min
6)RNA样品可直接用于后续实验或是冻于-80℃冰箱
2.绝对定量PCR
将RNA标准品进行10倍稀释,1×109,1×108,……1×104,每组样品重复两孔
绝对定量PCR体系
Fast Virus 1-Step Master Mix(4×) | 5μl |
引物1(50μM) | 0.1μl |
引物2(50μM) | 0.1μl |
探针(20μM) | 0.1μl |
核酸 | 5μl |
水 | 9.4μl |
PCR扩增程序:50℃,15min,95℃,3min;95℃,15s,60℃,45s+Plate Read,共50 个循环
扩增过程及荧光信号检测、数据的存储和分析均由荧光定量PCR仪及自带软件完成。
3.细胞活性检测
1)在96孔板中接种Vero细胞,37℃,5%CO2培养箱培养过夜
2)向培养板中加入不同浓度的药物(30,10,3.33,1.11,0.37,0.12,0.04,0.014μM)
3)将培养板在培养箱孵育24h
4)向每孔中加入10μl的CCK8溶液(注意不要在孔中生产气泡,它们会影响OD值的读数)
5)将培养板在培养箱内孵育1-4h
6)用酶标仪测定在450nm处的吸光度
7)若暂时不测定OD值,可以向每孔中加入10μl 0.1M的HCl溶液或者1%W/V SDS溶液,并遮盖培养板避光保存在室温条件下。24小时内测定,吸光度不会发生变化。
注意:如果待测物质有氧化性或还原性的话,可在加CCK-8之前更换新鲜培养基(除去培养基,并用培养基洗涤细胞两次,然后加入新的培养基),去掉药物影响。当然药物影响比较小的情况下,可以不更换培养基,直接扣除培养基中加入药物后的空白吸收即可。
活力计算
细胞活力(%)=[A(加药)-A(空白)]/[A(0加药)-A(空白)]×100
A(加药):具有细胞、CCK-8溶液和药物溶液的孔的吸光度
A(空白):具有培养基和CCK-8溶液而没有细胞的孔的吸光度
A(0加药):具有细胞、CCK-8溶液而没有药物溶液的孔的吸光度
细胞活力:细胞增殖活力或细胞毒性活力
Vero细胞加入不同浓度(30,10,3.33,1.11,0.37,0.12,0.04,0.014μM)的待测化合物,于37℃,5%CO2孵箱处理1h,之后加入0.1MOI的SARS-CoV-2病毒,继续37℃培养 1h。随后利用空白培养基洗细胞一遍,并加入上述还有不同浓度的(30,10,3.33,1.11,0.37,0.12,0.04,0.014μM)待测化合物,继续培养至病毒感染24h后,提取培养上清的RNA,并利用绝对定量PCR检测病毒拷贝数的变化,以0.014μM待测化合物处理的病毒拷贝数为最大感染值,其他浓度的拷贝数除以0.014μM组的拷贝数,得到病毒复制比例。利用 graphpad 7.0软件对数据进行非线性拟合(%inhibition),得到待测化合物的IC50。
Vero细胞加入不同浓度(30,10,3.33,1.11,0.37,0.12,0.04,0.014μM)的待测化合物,于37℃培养24h,之后利用CCK8试剂盒对细胞活性进行检测。利用graphpad 7.0软件对数据进行非线性拟合(%cell viability),得到待测化合物的CC50。
通过SI=CC50/IC50(CC50:cytotoxicity concentration,使50%细胞死亡时的药物浓度 IC50:inhibition concentration,半数抑制浓度),计算获得结果,具体数据如表1所示。
表1抑制SARS-CoV-2的药物的汇总
从数据中可以看出:对本领域技术人员而言,在药物的筛选过程中SI数值越高说明药物毒性越低,在筛药实验中SI一般大于10比较好,而上述药物中Nilotinib、Clofazimine、 Celecoxib、Actidione、Raloxifene HCl的SI都要远远的大于10,说明了上述几种药物有显著的药物应用前景,可以对其进行进一步的研究。
同时,从图1的结果中可以看出,随着加入化合物浓度增加,病毒毒价降低,呈剂量依赖性,给药物的制备提供了考量思路。若想让药物应用到临床上,其中一点就是药物本身的毒性要低,不会给人体带来太大的负作用。其中CC50越高,说明使50%细胞死亡的药物浓度越高;IC50越低,说明抑制效率达到50%的药物浓度越低;所以CC50越高,IC50越低,SI的值就越高,药物毒性就越低。
从表1分析可知,对于冠状病毒感染有效的药物属于广泛的药物治疗范畴,包括用于治疗神经性疾病、激素、离子通道、酶和一些抗菌剂等。
以上对本发明进行了详述。对于本领域技术人员来说,在不脱离本发明的宗旨和范围,以及无需进行不必要的实验情况下,可在等同参数、浓度和条件下,在较宽范围内实施本发明。虽然本发明给出了特殊的实施例,应该理解为,可以对本发明作进一步的改进。总之,按本发明的原理,本发明欲包括任何变更、用途或对本发明的改进,包括脱离了本发明中已公开范围,而用本领域已知的常规技术进行的改变。
Claims (1)
1.一种抑制新型冠状病毒SARS-CoV-2复制的药物组合物在制备治疗或预防新型冠状病毒SARS-CoV-2的药物中的用途,所述抑制新型冠状病毒SARS-CoV-2复制的药物组合物包括有效量的Vortioxetine;所述药物组合物还包括至少一种抗病毒剂或免疫调节剂,其中所述的抗病毒剂或免疫调节剂选自干扰素-α、洛匹那韦、利诺那韦、利巴韦林、磷酸氯喹、阿比多尔,所述药物组合物中还包括至少一种选自镇咳药,粘液溶解药,祛痰药,退热药,镇痛药或鼻减充血剂的药物,还包含在药学上可接受的载体。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111416989.0A CN114191552B (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010461381.9A CN111728973A (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
CN202111416989.0A CN114191552B (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010461381.9A Division CN111728973A (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114191552A CN114191552A (zh) | 2022-03-18 |
CN114191552B true CN114191552B (zh) | 2024-01-02 |
Family
ID=72647808
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111416996.0A Active CN114191553B (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
CN202111416989.0A Active CN114191552B (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
CN202010461381.9A Pending CN111728973A (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111416996.0A Active CN114191553B (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010461381.9A Pending CN111728973A (zh) | 2020-05-27 | 2020-05-27 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (3) | CN114191553B (zh) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021043234A1 (en) * | 2019-09-04 | 2021-03-11 | City University Of Hong Kong | Use of berbamine or its analogue for preventing or treating rna virus infection |
US11357771B2 (en) | 2019-09-04 | 2022-06-14 | City University Of Hong Kong | Methods of preventing or treating flavivirus virus infections and methods of inhibiting the entry of flvivirus, enterovirus or lentivirus into host cells |
CN114191553B (zh) * | 2020-05-27 | 2024-01-02 | 中国医学科学院病原生物学研究所 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
CN112137993A (zh) * | 2020-09-16 | 2020-12-29 | 南方医科大学 | 盐酸舍曲林及其衍生物在制备抗新型冠状病毒药物中的应用 |
CN112138006A (zh) * | 2020-10-08 | 2020-12-29 | 华中农业大学 | R848在制备抑制新型冠状病毒SARS-CoV-2药物中的应用 |
CN112315960B (zh) * | 2020-10-23 | 2021-08-13 | 武汉珈创生物技术股份有限公司 | 贝尼地平在制备抗新型冠状病毒感染性疾病的药物中的应用 |
CA3097717A1 (en) * | 2020-11-02 | 2022-05-02 | Skymount Medical Us Inc. | TYROSINE KINASE IN THE TREATMENT OF CORONAVIRUS DISEASES |
EP4000606A1 (en) * | 2020-11-18 | 2022-05-25 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Compounds for coronavirus infection treatment and/or prevention |
CN113735929A (zh) * | 2021-07-21 | 2021-12-03 | 海化生命(厦门)科技有限公司 | 一种抗冠状病毒的化合物及其制备方法与应用 |
EP4129287A1 (en) * | 2021-08-04 | 2023-02-08 | Dompe' Farmaceutici S.P.A. | Raloxifene for use in the treatment of sars-cov-2 variants infections |
WO2023036820A1 (en) * | 2021-09-10 | 2023-03-16 | H. Lundbeck A/S | Therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]piperazine |
CN114028453B (zh) * | 2021-12-07 | 2023-05-30 | 北京中医药大学 | 广谱抗病毒药物、及其药物组合物和应用 |
CN114632155B (zh) * | 2022-03-24 | 2022-10-11 | 中国人民解放军军事科学院军事医学研究院 | PKA siRNA在制备治疗新型冠状病毒病药物中的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104119298A (zh) * | 2014-08-13 | 2014-10-29 | 北京蓝贝望生物医药科技股份有限公司 | 氢溴酸沃赛汀或氢溴酸沃替西汀 |
US9399039B1 (en) * | 2015-06-30 | 2016-07-26 | University Of South Florida | Inhibitors of the FKBP51 protein from a high-throughput drug screen and methods of use |
CN114191553A (zh) * | 2020-05-27 | 2022-03-18 | 中国医学科学院病原生物学研究所 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101658523A (zh) * | 2008-04-01 | 2010-03-03 | 立业制药股份有限公司 | 一种氯法齐明用于治疗结核病的药物新用途 |
US10071062B2 (en) * | 2015-12-08 | 2018-09-11 | Cipla Limited | Methods for the treatment of hepatitis C |
US11649285B2 (en) * | 2016-08-03 | 2023-05-16 | Bio-Techne Corporation | Identification of VSIG3/VISTA as a novel immune checkpoint and use thereof for immunotherapy |
CN111150723A (zh) * | 2020-02-06 | 2020-05-15 | 北京佳诚医药有限公司 | 氨甲环酸注射液作为治疗肺炎药物的应用 |
CN111135184A (zh) * | 2020-03-05 | 2020-05-12 | 华中农业大学 | GS-441524在制备新型冠状病毒SARS-CoV-2抑制剂中的应用 |
-
2020
- 2020-05-27 CN CN202111416996.0A patent/CN114191553B/zh active Active
- 2020-05-27 CN CN202111416989.0A patent/CN114191552B/zh active Active
- 2020-05-27 CN CN202010461381.9A patent/CN111728973A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104119298A (zh) * | 2014-08-13 | 2014-10-29 | 北京蓝贝望生物医药科技股份有限公司 | 氢溴酸沃赛汀或氢溴酸沃替西汀 |
US9399039B1 (en) * | 2015-06-30 | 2016-07-26 | University Of South Florida | Inhibitors of the FKBP51 protein from a high-throughput drug screen and methods of use |
CN114191553A (zh) * | 2020-05-27 | 2022-03-18 | 中国医学科学院病原生物学研究所 | 抗新型冠状病毒SARS-CoV-2的药物及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN114191553A (zh) | 2022-03-18 |
CN114191552A (zh) | 2022-03-18 |
CN114191553B (zh) | 2024-01-02 |
CN111728973A (zh) | 2020-10-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114191553B (zh) | 抗新型冠状病毒SARS-CoV-2的药物及其应用 | |
JP2024003097A (ja) | コロナウイルス感染の治療におけるファビピラビルの使用 | |
CN116236580B (zh) | 金诺芬等老药及其组合物在抗单正链rna病毒中的应用 | |
US11376232B2 (en) | Vidofludimus for use in the treatment or prevention of viral diseases | |
US10894035B2 (en) | Use of indole compounds to stimulate the immune system | |
CN111743899B (zh) | 硝唑尼特及其活性形式替唑尼特在制备用于治疗SARS-CoV-2感染的药物中的应用 | |
CN113768917A (zh) | 木犀草素在抑制nlrp3炎症小体活化中的应用 | |
CN114028453B (zh) | 广谱抗病毒药物、及其药物组合物和应用 | |
CN111374985A (zh) | 盐酸非那吡啶的医药用途 | |
RU2597150C2 (ru) | Противовирусное соединение множественного действия, его состав и способ лечения вирусных заболеваний | |
Kaushik et al. | Glycolytic stress deteriorates 229E virulence to improve host defense response | |
RU2401121C1 (ru) | Фармацевтическая композиция для лечения и профилактики вирусных инфекций и сифилиса на основе экстрактов растительного происхождения и способ лечения и профилактики вирусных инфекций и сифилиса | |
JP2016525564A (ja) | 親油性スタチンと組合せ使用したメトトレキサートの効果向上 | |
CN113679701B (zh) | 邻苯三酚及其衍生物作为共价配体反应弹头的用途 | |
CN115317485B (zh) | 异莲心碱、甲基莲心碱在制备抗肝纤维化药物中的应用 | |
CN115721654B (zh) | 藜芦碱在制备抗冠状病毒的药物中的应用 | |
WO2023089862A1 (ja) | タマサキツヅラフジ由来アルカロイド含有製剤 | |
EP3344244A1 (en) | Use of indole compounds to stimulate the immune system | |
CN107540631A (zh) | 氨基羧酸酯类化合物在治疗寨卡病毒感染方面的应用 | |
JP6644917B2 (ja) | エンテロウイルス感染を治療する組成物および薬物併用方法 | |
CN117838697A (zh) | 巴瑞替尼在制备治疗流感病毒感染的药物中的应用 | |
CN117838689A (zh) | 培菲替尼在制备治疗流感病毒感染的药物中的应用 | |
Ghauri et al. | Debate on the Effectiveness of Hydroxychloroquine for Treatment of Coronavirus Disease 2019 (COVID-19) | |
CN114555089A (zh) | 用于乙型肝炎治疗的化合物 | |
KR100930480B1 (ko) | 신규 디아릴 헵타노이드계 화합물 및 그 용도 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |