CN1566142A - Polypeptide drug for inhibiting SARS coronavirus from infecting host cell - Google Patents
Polypeptide drug for inhibiting SARS coronavirus from infecting host cell Download PDFInfo
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- CN1566142A CN1566142A CN 03143037 CN03143037A CN1566142A CN 1566142 A CN1566142 A CN 1566142A CN 03143037 CN03143037 CN 03143037 CN 03143037 A CN03143037 A CN 03143037A CN 1566142 A CN1566142 A CN 1566142A
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Abstract
The invention relates to a polypeptide drug for inhibiting SARS coronavirus from infecting host cell, wherein the medicament has the general formula of X-SEQ-Z, wherein the SEQ is the No. 21 amino acid sequence represented by SEQ ID NO.1 - SEQ ID. 21. The pharmacodynamic experiment shows that the polypeptides medicament provided by the invention can be used to repress the SARS coronavirus infected host cells.
Description
Technical field
The present invention relates to a kind of SARS coronary virus resistant medicine, be specifically related to suppress the polypeptide class antiviral that sars coronavirus infects host cell.
Background technology
Sars coronavirus is the pathogenic agent that causes " atypical pneumonia " that broke out in 2003 in China and world wide, does not also have the specific medicine to treat at present.
SARS virus is a kind of coronavirus with cyst membrane, and the first step of its infected cell is exactly the fusion of virus envelope and host cell.The polypeptide class merges blocker molecule can the blocking virus cyst membrane because of it and the fusion of host cell, in the development of other virus drugs successful experience is arranged, and as HIV envelope protein GP41 two sections HR structural domains is arranged, and forms three N spirals and three C spirals respectively.Invade in the process of cell at HIV, these three N spirals and three C spiralization Coiled-coil six aggressiveness structures play crucial effects.Polypeptide drug T-20 (trade(brand)name Fuzeon) according to this principle design goes on the market, and it can block α spiralization six aggressiveness by GP41 itself effectively, thus the fusion of blocking-up HIV membrane structure and cytolemma.Studies show that the blocking ability of T-20 is strong, low to the body side effect, be a kind of ideal medicine.
The structural research of SARS envelope protein SPIKE shows that same existence can form two sections HR structural domains of Coiled-coil structure in SPIKE albumen.
Summary of the invention:
The objective of the invention is to develop the antiviral that class blocking-up sars coronavirus enters host cell.
Technical scheme of the present invention is to seek to play the material that sars coronavirus polypeptide class merges blocking effect, interaction by this material and SARS envelope protein Spike, stop the configuration of SARS envelope protein Spike to change, thereby the fusion of blocking virus cyst membrane and host cell reaches the purpose that prevention and treatment SARS virus infect.
Sars coronavirus polypeptide class provided by the invention merges the following general formula that has of blocking drugs:
X-SEQ-Z
Wherein, SEQ represents the polypeptide among the sars coronavirus envelope protein SPIKE, and described polypeptide comprises 21 aminoacid sequences shown in SEQ ID NO.1～SEQ ID NO.21.
In the polypeptide of 21 aminoacid sequences shown in SEQ ID NO.1～SEQ ID NO.21:
The non-peptide bond mode of connection is used in the connection of at least one amino-acid residue, for example, and with the form connection of imino-, ester, hydrazine, Urea,amino-or nitrogenous chemical bond;
At least one amino-acid residue exists with the D configuration;
Have an amino acid at least by another different amino-acid substitution, described substitute mode is that guard and/or not conservative;
Described polypeptide can be the homologue of the corresponding amino acid position of SARS spontaneous mutation strain;
Described polypeptide can be contained in one section other polypeptide;
Described polypeptide can be with monomer, dimer, and tripolymer and polymeric form exist.
X comprises amino, ethanoyl, and some hydrophobic grouping and macromolecular carrier group;
Z comprises carboxyl, amino and some hydrophobic grouping and macromolecular carrier group;
Described hydrophobic grouping comprises 9-fluorenylmethyloxycarbonyl (9-fluorenyl methoxy-carbonyl), carbobenzoxy-(Cbz) (carbobenzoxyl) dimethylaminon-aphthalene-5-sulfonyl (dansyl) and tertbutyloxycarbonyl (t-butyloxy carbonyl);
Described macromolecular carrier group is conjugated fatty acids (Lipid-fatty acid conjuate), polyoxyethylene glycol or carbohydrate group.
In the above-mentioned general formula, X and Z can not exist yet.That is, 21 aminoacid sequences shown in SEQ ID NO.1～SEQ ID NO.21 also can be used as the antiviral that the blocking-up sars coronavirus enters host cell.
Polypeptide of the present invention can obtain from eukaryotic cell expression system, procaryotic cell expression system or solid state chemistry synthetic approach.
In the experiment of adopting prokaryotic expression system, use one section sequence of the method amplification SARS envelope protein SPIKE of PCR earlier, it is cloned on the expression vector.Behind the abduction delivering, use GlutathioneSepharose 4B system purifying to obtain the polypeptide sample.
Chemosynthesis can be selected the routine operation method of present technique field artificial synthetic polypeptide for use.
Through the pharmacodynamic experiment test, polypeptide drug of the present invention infects its permissive cell VeroE6 for the sars coronavirus live virus and has blocking ability, shows that polypeptide drug of the present invention can suppress sars coronavirus and infect host cell.
Embodiment
In the polypeptide shown in 21 aminoacid sequences shown in SEQ ID NO.1 of the present invention～SEQ ID NO.21, SEQ ID NO.1～SEQ ID NO.15 adopts prokaryotic expression system to obtain, and SEQ ID NO.16～21 obtain for synthetic.
Embodiment 1 escherichia coli expression polypeptide
1.SARS the extraction of total RNA of Virus Sample
(1) contains the SARS virus sample with 1ml trizol (GIBCO) extracting;
(2) add 200 μ l chloroforms, thermal agitation 15 seconds;
(3) room temperature leaves standstill 3-5min, 10000g4 ℃ of centrifugal 15min;
(4) sucking-off 500 μ l waters are transferred in the new pipe;
(5) add 500 μ l Virahols, mixing fully vibrates; Room temperature leaves standstill 10min
(6) 10000g4 ℃ of centrifugal 10min obtains SARS virus RNA precipitation.
2.SARS the clone of viral SPIKE protein gene
(1) be DNA with the reverse transcription of SARS virus rna gene group
Reverse transcription primer: SPIKE albumen antisense primer
ThermoScript II: MMLV-RT (promega)
(2) amplify the dna sequence dna of SPIKE by PCR method.
Amplimer:
Sense：5’-cgggatccaacgaacatgtttattttcttattatttc-3’
antisense：5’-cggaattcgtttatgtgtaatgtaatttgacaccc-3’
(3) the PCR product is connected in the pcDNA3.1+ carrier
Mode of connection: BamHI cuts connection for EcoRI pair.
3. the sequence and the PCR primer thereof of cloning the polypeptide that obtains following SEQ ID NO.1～SEQ ID NO.15 are as follows:
SEQ?ID?NO.1：NGIGVTQNVLYENQKQIANQFNKAISQIQESLTTTSTA
AATGGCATTGGAGTTACC
TGC?AGT?TGA?TGT?TGT?TGT?AAG
SEQ?ID?NO.2：PDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQ
CCAGATGTTGATCTTGGC
TTGAAGGTCAATGAGTGATTC
SEQ?ID?NO.3：GDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQ
GGCGACATTTCAGGCATTAAC
TTGAAGGTCAATGAGTGATTC
SEQ?ID?NO.4：ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPW
A?TTT?CAG?GCA?TTA?ACG?CTT?C
CCAAGGCCATTTAATATATTGC
SEQ?ID?NO.5：INASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPW
ATTAACGCTTCTGTCGTCAAC
CCAAGGCCATTTAATATATTGC
SEQ?ID?NO.6：VVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPW
G?TCG?TCA?ACA?TTC?AAA?AAG
CCAAGGCCATTTAATATATTGC
SEQ?ID?NO.7：IQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPW
A?TTC?AAA?AAG?AAA?TTG?ACC?GC
CCAAGGCCATTTAATATATTGC
SEQ?ID?NO.8：IDRLNEVAKNLNESLIDLQELGKYEQYIKWPW
A?TTG?ACC?GCC?TCA?ATG?AGG?TC
CCAAGGCCATTTAATATATTGC
SEQ?ID?NO.9：ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGK
A?TTT?CAG?GCA?TTA?ACG?CTT?C
TTTTCCCAATTCTTGAAG
SEQ?ID?NO.10：INASVVNIQKEIDRLNEVAKNLNESLIDLQELGK
ATTAACGCTTCTGTCGTCAAC
TTTTCCCAATTCTTGAAG
SEQ?ID?NO.11：VVNIQKEIDRLNEVAKNLNESLIDLQELGK
G?TCG?TCA?ACA?TTC?AAA?AAG
TTTTCCCAATTCTTGAAG
SEQ?ID?NO.12：IQKEIDRLNEVAKNLNESLIDLQELGK
A?TTC?AAA?AAG?AAA?TTG?ACC?GC
TTTTCCCAATTCTTGAAG
SEQ?ID?NO.13：ISGINASVVNIQKEIDRLNEVAKNLNESLIDL
A?TTT?CAG?GCA?TTA?ACG?CTT?C
AAG?GTC?AAT?GAG?TGA?TTC?A
SEQ?ID?NO.14：INASVVNIQKEIDRLNEVAKNLNESLIDL
ATTAACGCTTCTGTCGTCAAC
AAG?GTC?AAT?GAG?TGA?TTC?A
SEQ?ID?NO.15：VVNIQKEIDRLNEVAKNLNESLIDL
G?TCG?TCA?ACA?TTC?AAA?AAG
AAG?GTC?AAT?GAG?TGA?TTC?A
4, polypeptide expression
(1) will be connected to the pGEX-6p-2 carrier behind the PCR product recovery purifying
The sma I point of contact of (Amersham Pharmacia Biotech.27-4598-01).
(2) recombinant plasmid that will correctly make up is transferred in JM109 (DE3) competent cell, with containing antibiotic LB substratum incubated overnight.
(3) overnight culture connects the 400ml fresh culture at 1: 50, adds 80ml 1M IPTG after 2 hours and induces, and continues to cultivate 4 hours.
(4) 4 ℃, the bacterium of the centrifugal cultivation of 8000rpm 6min adds the resuspended precipitation of 15ml Lysis Buffer, and adding N,O-Diacetylmuramidase to final concentration is 100mg/ml, puts 30min on ice, ultrasonic on ice 12 times (300W, 10s/10s)
(5) 4 ℃, the centrifugal 15min of 12000rpm, get the ratio adding Glutathione Sepharose 4B (Amersham Pharmacia Biotech.17-0756-01) of supernatant with 5-10mgGST/ml, on ice in conjunction with 1h, make sample liquid cross the Hepes500 washing GST pillar that chromatography column (Bio-Rad 74306) uses 5 times of volumes, use the Hepes100 washing of 10 times of volumes afterwards, contain the Hepes100 washing column material 4 times of 10mMGSH again with 0.5ml, collect effluent liquid.
(6) cut the whole dialysed overnight of Buffer at enzyme, remove GSH, use spectrophotometer quantitatively (1OD280=0.5mg/ml), add 1ml (2units) preScissionProtease (Amersham Pharmacia Biotech.27-0843-01) according to every 100mg, 4 ℃ of enzymes are cut 3h.Ratio with 5-10mg GST/ml adds Glutathione Sepharose 4B (Amersham PharmaciaBiotech.17-0756-01), on ice in conjunction with 1h, make sample liquid cross chromatography column (Bio-Rad74306), collect effluent liquid, use the 0.5ml enzyme to cut Buffer and wash again once, collect effluent liquid.
Embodiment 2 polypeptide suppress the experiment of SARS virus target cell infection
One, experiment material and method
The obtaining and cultivating of 1 virus
Get the supernatant that contains SARS virus and be added on the VeroE6 cell that grows up to individual layer, 37 ℃ were infected 1 hour, added DMEM+2%FBS, continued at 37 ℃ and cultivated observation CPE, treated to gather in the crops when CPE is complete supernatant.
The mensuration of 2 virus titers
With viral supernatant serial dilution, will have only half cell sample CPE to occur, and next extent of dilution there is not the extent of dilution of CPE to be decided to be greatest dilution.
3 measure the inhibition activity of polypeptide to virus
Every part of test cell adds polypeptide sample final concentration 1 μ M, adds viral 200TCID50, observes CPE after 24 hours and judges whether cell is infected.
Two, experimental result
Observed not infected to the CPE cell, prove that being tried polypeptide sars coronavirus capable of blocking enters host cell.
Sequence table
＜110〉Peking University
＜120〉suppress the polypeptide drug that sars coronavirus infects host cell
<130>03-01
<160>19
<170>PatentIn?version?3.1
<210>1
<211>38
<212>PRT
＜213〉sars coronavirus
<400>1
Asn?Gly?Ile?Gly?Val?Thr?Gln?Asn?Val?Leu?Tyr?Glu?Asn?Gln?Lys?Gln
1 5 10 15
Ile?Ala?Asn?Gln?Phe?Asn?Lys?Ala?Ile?Ser?Gln?Ile?Gln?Glu?Ser?Leu
20 25 30
Thr?Thr?Thr?Ser?Thr?Ala
35
<210>2
<211>40
<212>PRT
＜213〉sars coronavirus
<400>2
Pro?Asp?Val?Asp?Leu?Gly?Asp?Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val
1 5 10 15
Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu
20 25 30
Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln
35 40
<210>3
<211>35
<212>PRT
＜213〉sars coronavirus
<400>3
Gly?Asp?Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu
1 5 10 15
Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile
20 25 30
Asp?Leu?Gln
35
<210>4
<211>46
<212>PRT
＜213〉sars coronavirus
<400>4
Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp
1 5 10 15
Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25 30
Gln?Glu?Leu?Gly?Lys?Tyr?Glu?Gln?Tyr?Ile?Lys?Trp?Pro?Trp
35 40 45
<210>5
<211>43
<212>PRT
＜213〉sars coronavirus
<400>5
Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn
1 5 10 15
Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu
20 25 30
Gly?Lys?Tyr?Glu?Gln?Tyr?Ile?Lys?Trp?Pro?Trp
35 40
<210>6
<211>39
<212>PRT
＜213〉sars coronavirus
<400>6
Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys
1 5 10 15
Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys?Tyr?Glu
20 25 30
Gln?Tyr?Ile?Lys?Trp?Pro?Trp
35
<2l0>7
<211>36
<212>PRT
＜213〉sars coronavirus
<400>7
Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn
1 5 10 15
Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys?Tyr?Glu?Gln?Tyr?Ile
20 25 30
Lys?Trp?Pro?Trp
35
<210>8
<211>32
<212>PRT
＜213〉sars coronavirus
<400>8
Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile
1 5 10 15
Asp?Leu?Gln?Glu?Leu?Gly?Lys?Tyr?Glu?Gln?Tyr?Ile?Lys?Trp?Pro?Trp
20 25 30
<210>9
<211>37
<212>PRT
＜213〉sars coronavirus
<400>9
Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp
1 5 10 15
Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25 30
Gln?Glu?Leu?Gly?Lys
35
<210>10
<211>34
<212>PRT
＜213〉sars coronavirus
<400>10
Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn
1 5 10 15
Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu
20 25 30
Gly?Lys
<210>11
<211>30
<212>PRT
＜213〉sars coronavirus
<400>11
Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys
1 5 10 15
Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys
20 25 30
<210>12
<211>27
<212>PRT
＜213〉sars coronavirus
<400>12
Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn
1 5 10 15
Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys
20 25
<210>13
<211>32
<212>PRT
＜213〉sars coronavirus
<400>13
Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp
1 5 10 15
Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25 30
<210>14
<211>29
<212>PRT
＜213〉sars coronavirus
<400>14
Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn
1 5 10 15
Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25
<210>15
<211>25
<212>PRT
＜213〉sars coronavirus
<400>15
Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys
1 5 10 15
Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25
<210>16
<211>35
<212>PRT
＜213〉sars coronavirus
<400>16
Leu?Gly?Asp?Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys
1 5 10 15
Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu
20 25 30
Ile?Asp?Leu
35
<210>17
<211>35
<212>PRT
＜213〉sars coronavirus
<400>17
Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu
1 5 10 15
Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys?Tyr?Glu?Gln?Tyr?Ile?Lys
20 25 30
Trp?Pro?Trp
35
<210>18
<211>36
<212>PRT
＜213〉sars coronavirus
<400>18
Ile?Asp?Arg?Leu?Ile?Thr?Gly?Arg?Leu?Gln?Ser?Leu?Gln?Thr?Tyr?Val
1 5 10 15
Thr?Gln?Gln?Leu?Ile?Arg?Ala?Ala?Glu?Ile?Arg?Ala?Ser?Ala?Asn?Leu
20 25 30
Ala?Ala?Thr?Lys
35
<210>19
<211>36
<212>PRT
＜213〉sars coronavirus
<400>19
Gln?Asn?Val?Leu?Tyr?Glu?Asn?Gln?Lys?Gln?Ile?Ala?Asn?Gln?Phe?Asn
1 5 10 15
Lys?Ala?Ile?Ser?Gln?Ile?Gln?Glu?Ser?Leu?Thr?Thr?Thr?Ser?Thr?Ala
20 25 30
Leu?Gly?Lys?Leu
35
<210>20
<211>35
<212>PRT
＜213〉sars coronavirus
<400>20
Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp?Arg?Leu?Asn?Glu?Val?Ala?Lys
1 5 10 15
Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu?Gln?Glu?Leu?Gly?Lys?Tyr?Glu
20 25 30
Gln?Tyr?Ile
35
<210>21
<211>35
<212>PRT
＜213〉sars coronavirus
<400>21
Ile?Ser?Gly?Ile?Asn?Ala?Ser?Val?Val?Asn?Ile?Gln?Lys?Glu?Ile?Asp
1 5 10 15
Arg?Leu?Asn?Glu?Val?Ala?Lys?Asn?Leu?Asn?Glu?Ser?Leu?Ile?Asp?Leu
20 25 30
Gln?Glu?Leu
35
Claims (10)
1. suppress the polypeptide drug that sars coronavirus infects host cell, have following general formula:
X-SEQ-Z
In the formula, SEQ represents the polypeptide among the sars coronavirus envelope protein SPIKE, and described polypeptide comprises 21 aminoacid sequences shown in SEQ ID NO.1～SEQ ID NO.21;
X comprises amino, ethanoyl and hydrophobic grouping and macromolecular carrier group;
Z comprises carboxyl, amino and hydrophobic grouping and macromolecular carrier group.
2. the described polypeptide drug of claim 1, the non-peptide bond mode of connection is used in the connection of at least one amino-acid residue of wherein said polypeptide; Described non-peptide bond mode of connection comprises that the form with imino-, ester, hydrazine, Urea,amino-or nitrogenous chemical bond connects.
3. the described polypeptide drug of claim 1, at least one amino-acid residue of wherein said polypeptide exists with the D configuration.
4. the described polypeptide drug of claim 1, at least one amino acid of wherein said polypeptide are by another different amino-acid substitution, and described substitute mode is that guard and/or conservative.
5. the described polypeptide drug of claim 1, wherein said polypeptide is the homologue of the corresponding amino acid position of SARS spontaneous mutation strain.
6. the described polypeptide drug of claim 1, wherein said polypeptide is comprised in one section other polypeptide.
7. the described polypeptide drug of claim 1, the form of wherein said polypeptide comprises monomer, dimer, tripolymer and polymer.
8. the purposes of the described polypeptide drug of claim 1 in preparation prevention and treatment sars coronavirus medicine.
9. has polypeptide of sequence shown in SEQ ID NO.1～SEQ ID NO.21.
10. the purposes of the described polypeptide of claim 9 in preparation prevention and treatment sars coronavirus medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143037 CN1249083C (en) | 2003-06-12 | 2003-06-12 | Polypeptide drug for inhibiting SARS coronavirus from infecting host cell |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143037 CN1249083C (en) | 2003-06-12 | 2003-06-12 | Polypeptide drug for inhibiting SARS coronavirus from infecting host cell |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1566142A true CN1566142A (en) | 2005-01-19 |
| CN1249083C CN1249083C (en) | 2006-04-05 |
Family
ID=34471245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03143037 Expired - Fee Related CN1249083C (en) | 2003-06-12 | 2003-06-12 | Polypeptide drug for inhibiting SARS coronavirus from infecting host cell |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1249083C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111675752A (en) * | 2020-03-16 | 2020-09-18 | 成都奥达生物科技有限公司 | Coronavirus membrane fusion inhibitor and pharmaceutical application thereof |
| CN114437184A (en) * | 2021-08-16 | 2022-05-06 | 中国科学院微生物研究所 | Polypeptide for resisting novel coronavirus and application thereof |
-
2003
- 2003-06-12 CN CN 03143037 patent/CN1249083C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111675752A (en) * | 2020-03-16 | 2020-09-18 | 成都奥达生物科技有限公司 | Coronavirus membrane fusion inhibitor and pharmaceutical application thereof |
| CN111675752B (en) * | 2020-03-16 | 2023-07-07 | 成都奥达生物科技有限公司 | Coronavirus membrane fusion inhibitor and pharmaceutical application thereof |
| CN114437184A (en) * | 2021-08-16 | 2022-05-06 | 中国科学院微生物研究所 | Polypeptide for resisting novel coronavirus and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1249083C (en) | 2006-04-05 |
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