WO2012000459A1 - Polypeptide anti-infection par le vih, composition et utilisation - Google Patents

Polypeptide anti-infection par le vih, composition et utilisation Download PDF

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Publication number
WO2012000459A1
WO2012000459A1 PCT/CN2011/076812 CN2011076812W WO2012000459A1 WO 2012000459 A1 WO2012000459 A1 WO 2012000459A1 CN 2011076812 W CN2011076812 W CN 2011076812W WO 2012000459 A1 WO2012000459 A1 WO 2012000459A1
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seq
polypeptide
formula
derivative
natural
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PCT/CN2011/076812
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English (en)
Chinese (zh)
Inventor
刘克良
姜世勃
史卫国
贾启燕
白玉
冯思良
蔡利锋
王潮
张沙
姜喜凤
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中国人民解放军军事医学科学院毒物药物研究所
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Publication of WO2012000459A1 publication Critical patent/WO2012000459A1/fr

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    • 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
    • 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
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/73—Fusion polypeptide containing domain for protein-protein interaction containing coiled-coiled motif (leucine zippers)
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16033—Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/16011—Human Immunodeficiency Virus, HIV
    • C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • Anti-H I V infected polypeptide composition and use thereof
  • the present invention belongs to the field of biomedicine and relates to a polypeptide which is resistant to HIV infection and, in particular, to a polypeptide represented by the formula I, a derivative thereof, a stereoisomer thereof, or a salt thereof which is not physiologically toxic.
  • the present invention also relates to a pharmaceutical composition comprising the above-described polypeptide of the formula I, a derivative thereof, a stereoisomer thereof, or a salt thereof which is not physiologically toxic, and a polypeptide of the formula I, a derivative thereof, a stereoisomer thereof, or The use of non-physiological salts in the treatment or prevention of diseases associated with HIV infection, especially acquired immunodeficiency syndrome (AIDS).
  • AIDS acquired immunodeficiency syndrome
  • HIV fus ion inhibitors are a new class of anti-HIV drugs that interfere with the entry of viruses into target cells. Unlike traditional enzyme inhibitors, they act outside the cell and cut off the spread of the virus at the initial stage of infection. It has special significance for the prevention and control of HIV-1 infection, and thus has become a hot spot for new mechanisms for anti-HIV drug research.
  • HIV fusion inhibitors target the HIV-1 fusion protein gp41, a functional protein that mediates the fusion of HIV-1 to target cell membranes. HIV fusion inhibitors inhibit the formation of core hexamer structures (6-HB) by membrane fusion by inhibiting gp41, thereby inhibiting virus entry into target cells.
  • T-20 is the first and currently the only listed HIV-1 A fusion inhibitor, a native sequence 36 peptide (referred to as a C-peptide) derived from the HIV-1 gp41 HR2 domain, was approved by the FDA in 2003.
  • T20 binds to gp41, which competitively inhibits the formation of functional core structures that are mediated by gp41, blocks the fusion of HIV-1 with target cell membranes, and inhibits viral infection of target cells.
  • T20 is completely derived from the gp41 natural sequence, it is highly sensitive to target mutations. A single amino acid residue mutation in the target sequence will result in a 10-fold decrease in T20 activity, and two residue mutations will make it The activity is reduced by a factor of 100. Therefore, although the natural sequence of T20 maintains the structure of the natural ligand to the utmost extent, it also causes the virus to be susceptible to T20 due to the high mutation of the target HIV-1 gp41 sequence. Secondly, T20 is easily degraded by proteases and has low bioavailability in vivo. Therefore, how to overcome drug resistance and improve the stability of enzymatic hydrolysis is the main direction of research on a new generation of HIV fusion inhibitors.
  • HIV-1 peptide fusion inhibitors are primarily based on optimization and modification of the active natural ligand sequence.
  • the first generation fusion inhibitors T-20, C34, etc. are directly derived from the native sequence of gp41 HR2; the second generation T1249, Sifuvirtide, T1144, etc. are in the natural sequence?
  • the non-conservative acid residues are deleted and replaced.
  • the design based on natural ligand sequences is reasonable and feasible, but due to the high sensitivity of natural origin sequences to drug resistance mutations, this design has certain limitations.
  • the present inventors proposed an anti-HIV active peptide design idea based on a non-naturally occurring sequence of a target structure: based on the three-dimensional crystal structure of the target gp41 HR1 spiral trimer, using a computer-aided rational design method, de novo design is not natural
  • the sequence (X-spiral peptide, which mimics the active conformation of the native C-peptide, binds to the target to produce the corresponding biological function, thereby designing a novel structure of the anti-HIV active polypeptide.
  • a new way of inhibiting drug resistance is explored by using non-native sequences that are completely non-homologous to native sequences. The present invention has thus been completed. Summary of the invention
  • the object of the present invention is to design a novel completely non-native sequence of an anti-HIV-infected polypeptide, and to have an HIV infection-infecting activity comparable to or higher than the native sequence, and to inhibit the T20-resistant HIV strain.
  • One aspect of the invention relates to a polypeptide of formula I, a derivative thereof, a stereoisomer thereof, or a salt thereof which is not physiologically toxic,
  • X bi , X b2 , X b3 are each independently a D- or L-type natural or non-natural acidic amino acid or a hydrophilic amino acid;
  • X b4 is a D or L type natural or non-natural acidic amino acid or hydrophobic amino acid
  • Xei. X e2 , X e3 , X e4 are independently D- or L-type natural or non-natural hydrophobic amino acids;
  • X d3 and X d4 are each independently a D- or L-type natural or non-natural hydrophobic or hydrophilic amino acid
  • X a4 is a D or L type natural or non-natural hydrophilic amino acid
  • B is a D- or L-type natural or non-natural basic amino acid
  • L is a peptide sequence of 7 to 14 acid residues acting on a lipid membrane, cholesterol, or a long-chain fatty acid having 6 or more carbon atoms, or L-deletion.
  • L is selected from the group consisting of: MEWDRE- (complete sequence corresponding to SEQ ID NO: 4), WEEWDKK- (complete sequence corresponding to SEQ ID NO: 49), WEEWRKK- (complete sequence corresponding SEQ ID NO: 50), WEEWAKK (complete sequence corresponds to SEQ ID NO: 51), WEEWIKK- (complete sequence corresponds to SEQ ID NO: 52), WEEWSKK- (complete sequence corresponds to SEQ ID NO: 53), TWMEWDRE - (complete sequence corresponds to SEQ ID NO: 36), MT MEWDRE- (complete sequence corresponds to SEQ ID NO: 37), NMT MEWDRE- (complete sequence corresponds to SEQ ID NO: 38), NNMTWMEWDRE- (complete sequence corresponds to SEQ ID NO: 39), WNNMTWMEWDRE- (complete sequence corresponds to SEQ ID NO: 40), IWNNMTWMEWDRE- (complete sequence corresponds to SEQ ID NO: 41), and QI WNNMTWMEWDRE-
  • X bl , X b2 , X b3 , X b4 are each independently selected from the group consisting of D-type or L-type amino acids: glutamic acid (E), glutamine (Q), asparagine (N), serine (S ), threonine (T), and tyrosine (Y);
  • X el , X e2 , X e3 , X e4 are each independently selected from the group consisting of D-type or L-type amino acids: isoleucine (I), valine (V), norleucine (Nle), Leucine (L), and alanine (A);
  • X d3 and X d4 are each independently selected from the group consisting of D type or L type of the following amino acids: leucine (L), norleucine (Nle), glutamine (Q), asparagine (N), and Serine (S);
  • X a4 is selected from the following basic acids of type D or L: serine (S), glutamine (Q), asparagine (N);
  • B is selected from D-type or L-form lysine (K) or arginine (R);
  • L is selected from the following sequences or small molecules: - WASLWNWF (complete sequence corresponding to SEQ ID NO: 43), cholesterol, and CH 3 (CH 2 ) n C00H, wherein n is 4-16 An integer; preferably, n is 6, 10, 12, 14, 16.
  • polypeptide of Formula I a derivative thereof, a stereoisomer thereof, or a salt thereof that is not physiologically toxic, wherein the polypeptide of Formula I is selected from the group consisting of:
  • WMEWDRE IEELIRR SEELIRR IEEQIRR QEESIRR (SEQ ID NO: 5)
  • WMEWDRE IEELIKK SEELAKK IEEQIKK QEESIKK ( SEQ ID NO: 11)
  • AEELAKK AEELAKK AEELAKK AEELAKK ASL N F (SEQ ID NO: 13)
  • RGDIEEFAKK SEELAKK IEELAKK AEELAKK WASLWNWF ( SEQ ID NO: 34 );
  • NMT ME DRE IEELIKK SEELIKK lEEQIKK QEESIKK SEQ ID NO: 38 );
  • WMEWDRE IEELIKK SEELIKK lEEQIKK QEESAKK (SEQ ID NO: 48) 49.
  • EE DKK I EEL IKK SEEL IKK IEEQIKK QEESIKK ( SEQ ID NO: 49 ) ;
  • the polypeptide of Formula I, a derivative thereof, a stereoisomer thereof, or a salt thereof that is not physiologically toxic is selected from the above compounds 2 - 9, 20, 24 - 26, 30 - 34 and 44 - 53.
  • Another aspect of the invention relates to a pharmaceutical composition comprising at least one of the above-described polypeptides of formula I, derivatives thereof, stereoisomers thereof, or salts thereof which are not physiologically toxic, and pharmaceutically acceptable carriers or Excipients.
  • a further aspect of the invention relates to an HIV fusion inhibitor comprising at least one of the above-described polypeptides of formula I, derivatives thereof, stereoisomers thereof, or salts thereof which are not physiologically toxic.
  • a further aspect of the invention relates to the use of a polypeptide of the above formula I, a derivative thereof, a stereoisomer thereof, or a salt thereof which is not physiologically toxic, for the preparation of an HIV fusion inhibitor.
  • a further aspect of the invention relates to a polypeptide of the above formula I, a derivative thereof, The use of an isomer, or a physiologically toxic salt thereof, for the manufacture of a medicament for the treatment or prevention of a disease associated with HIV infection, particularly AIDS.
  • a further aspect of the invention relates to a method of treating or preventing a disease associated with HIV infection, in particular AIDS, comprising administering an effective amount of a polypeptide of formula I, a derivative thereof, or a stereoisomer thereof to a subject to be treated or prevented.
  • the term "natural” refers to a naturally occurring, unmodified, such as the amino acid sequence of HIV-1 gp41 itself.
  • non-native means artificially designed, different from nature, such as modified, modified sequences of directly derived natural sequences, and the like.
  • hydrophobic amino acid means an acid having a hydrophobic chain in the side chain, and includes: Ala, Val, Leu, He, Met, Phe, Trp and the like.
  • hydrophilic amino acid means an acid having a hydrophilic group capable of forming a hydrogen bond with water, including: Ser, Thr, Cys, Asp, Asn, Glu, Gin , Arg, Lys, His, Tyr, etc.
  • the term "acidic amino acid” means an amino acid having a carboxyl group in a side chain, and includes: Glu, Asp and the like.
  • basic acid means an amino acid having a side chain containing a thiol group, and includes: Lys, Arg and the like.
  • the term "acting with a lipid membrane” means a hydrophobic group or peptide sequence capable of interacting with a lipid bilayer of a cell membrane, including: cholesterol, long-chain fatty acids and the like.
  • Env envelope glycoprotein
  • HIV Human Immunodeficiency Virus
  • HIV-1 human immunodeficiency virus type I HIV-1 human immunodeficiency virus type I
  • Trp Tryptophan
  • the solid phase synthesis carrier Rink amide resin used in the examples is Tianjin Nankai Synthetic Co., Ltd.; HBTU, H0BT, DIEA and Fmoc protected natural amino acids or D-type non-natural amino acids are Shanghai Jill Biochemical Co., Ltd. and Chengdu Chengnuo New Technology Co., Ltd. products.
  • N-methylpyrrolidone (leg P) is a product of ACR0S; trifluoroacetic acid (TFA) is a product of Beijing Bomaijie Technology Co., Ltd.; DMF and DCM are products of South Korea's Samsung; chromatographic pure acetonitrile is Fisher's product.
  • Other reagents are domestically produced pure products if they are not described.
  • a standard Fmoc solid phase peptide synthesis method was employed. All peptide sequences were acylated at the C-terminus and acetylated at the N-terminus.
  • Rink Amide resin is used, and the amino acid is L-case, and the peptide chain is extended from the C-terminus to the N-terminus.
  • the condensing agent is HBTU/H0Bt/DIEA.
  • the deprotecting agent gas is gas acid acid piperidine / DMF solution.
  • the cleavage agent is trifluoroacetic acid (TFA), and the crude peptide is dissolved in water and lyophilized.
  • microwave peptide synthesis conditions are as follows:
  • Deprotecting agent 20% v/v piperidine in DMF solution
  • Blocking reagent 20% v/v acetic anhydride in DMF solution.
  • Peptide resin cleavage Weighed 2. 05g of peptide resin synthesized by microwave synthesizer, placed in a 250ml eggplant-shaped bottle, ice bath, electromagnetic stirring. The lysate was prepared by adding 1 gram of the peptide resin to 10 ml. TFA needs to be cooled in the ice bath for 30 minutes in advance or stored in the refrigerator in advance; the prepared lysate is added to the peptide resin under ice bath conditions, electromagnetic stirring, the resin turns orange-red, and the reaction is carried out under ice bath for 30 minutes, then, withdraw The reaction was stirred for 90 min at room temperature and the reaction was completed.
  • the crude peptide obtained was purified by medium pressure or high pressure chromatography.
  • the color column is a C18 column, and the eluent is acetonitrile, 7j and a small amount of acetic acid.
  • Example 45 Inhibition of HIV-1 bioactivity assay
  • HIV-1 mediated cell-cell fusion activity evaluation (IC 5 ).
  • HI V-1 mediated cell-cell fusion by staining transfer assay HIV-1 IB- infected H9 cells (H9/HIV) - 1 uncomfortable IB ) was labeled with a fluorescent reagent, Calcein-AM (Molecular Probes, Inc., Eugene, OR), and then 50 ⁇ l of labeled H9/HIV-l mB cells (2 x) were added to each well in a 96-well plate.
  • test samples the compounds prepared in Test Examples 1-34 and 44-53, diluted from 25 ( ⁇ g/ml concentration twice gradient), 37 for 30 min; then MT-2 cells were added to each well at 100 u 1 (1 x 107 ml) and 37 for 2 h. Fusion and unfused
  • MT-2 Calcein-labeled HIV-1 infected MT-2 cells (MT-2 is a commonly used effector cell, used in this experiment to mimic HIV-infected target cells, commercially available) using reverse fluorescence microscopy (Zeiss, Germany) count. Calculate IC 5 . value.
  • the sandwich ELISA method detects the C peptide (C peptide is an abbreviation for a polypeptide derived from the gp41 CHR functional region, and is a term well known in the art, and all compounds in the present invention belong to the C peptide range.)
  • Inhibition of gp41 6-HB formation activity Test compounds (Examples 1 - 34 Preparation The compound was diluted from 25 ( ⁇ g/ml concentration twice).
  • ⁇ 36 peptide similar to the C peptide, which is derived from the polypeptide of the gp41 NHR region, N36 is a kind of N peptide, which is well known in the research field.
  • test compound compounds 1-34 and 44-53 all showed a certain degree of inhibition of HIV-1 mediated cell fusion and inhibition of 6-HB formation activity.
  • compounds 4, 49, 50, 51, 52, 53 inhibit HIV-1 mediated cell fusion activity levels comparable to T-20 and C34.
  • Example 46 Inhibition of T-20-resistant virus strain by non-native HR sequence
  • the HIV-1 capsid protein p24 content was determined by ELISA. The effect of HR sequence on T-20 resistant strain was determined.
  • the 96-well polystyrene plate was coated with HIVIG in a buffer solution of 0. 85 M carbonate (pH 9. 6), overnight at 4 ° C, and then PBS-T buffer (0.01 M PBS, containing 0.05). % Tween-20) Wash and block with PBS solution containing 1% dry skim milk.
  • the HIV-1 virus lysate was added to the well and incubated for 37 hours for 1 hour.
  • Anti-p24 mAb (183-12H-5C), biotinylated mouse anti-IgGl, SA-HRP and TMB were added continuously. After completion of the reaction, the reaction was terminated with a 1 N H 2 SO 4 stop solution. The absorbance at 450 nm was recorded with a microplate reader. Calculate the IC50 value. The results are shown in Table 2. HR sequence peptide inhibits T- 20 resistant strain activity
  • aNL4-3 D36G is a T-20 sensitive virus forest, and NL4-3 (36G) V38A/N42T and NL4-3 (36G) V38E/N42S derived from it are T-20 resistant mutant virus forests. Each sample was tested 3 times.

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  • AIDS & HIV (AREA)
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Abstract

La présente invention concerne le domaine biomédical, porte sur un polypeptide anti-infection par le VIH et porte spécifiquement sur un polypeptide représenté par Y1-IXb1ELXe1BB-SXb2ELXe2BB-IXb3EXd3Xe3BB-Xa4Xb4EXd4Xe4BB-Y2 (formule I), un dérivé de celui-ci, un isomère tridimensionnel de celui-ci ou un sel non toxique physiologiquement acceptable de celui-ci. La présente invention porte également sur une composition pharmaceutique contenant le polypeptide représenté par la formule (I), le dérivé de celui-ci, l'isomère tridimensionnel de celui-ci ou le sel non toxique physiologiquement acceptable de celui-ci. La présente invention porte également sur l'utilisation du polypeptide représenté par la formule (I), du dérivé de celui-ci, sur l'isomère tridimensionnel de celui-ci ou du sel non toxique physiologiquement acceptable de celui-ci dans le traitement ou la prévention de maladies induites par une infection par le VIH, en particulier le syndrome d'immunodéficience acquise (SIDA).
PCT/CN2011/076812 2010-07-02 2011-07-04 Polypeptide anti-infection par le vih, composition et utilisation WO2012000459A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019223642A1 (fr) * 2018-05-23 2019-11-28 中国人民解放军军事科学院军事医学研究院 Polypeptide antiviral, composition pharmaceutique et utilisation associées

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103122025B (zh) * 2011-11-21 2017-09-05 中国人民解放军军事医学科学院毒物药物研究所 抑制hiv感染的小分子‑多肽缀合物
CN106139150B (zh) * 2015-04-10 2019-10-08 复旦大学 一种艾滋病治疗性疫苗组合物及其应用
CN106397548A (zh) * 2015-07-29 2017-02-15 复旦大学 用于抑制hiv感染的多肽及其药物用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010019717A2 (fr) * 2008-08-13 2010-02-18 New York Blood Center Thérapie de combinaison d'inhibiteurs de fusion/entrée du vih ciblant gp41

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010019717A2 (fr) * 2008-08-13 2010-02-18 New York Blood Center Thérapie de combinaison d'inhibiteurs de fusion/entrée du vih ciblant gp41

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
IZUMI, KAZUKI ET AL.: "Design of Peptide-based Inhibitors for Human Immunodeficiency Virus Type 1 Strains Resistant to T-20.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 284, no. 8, 20 February 2009 (2009-02-20), pages 4914 - 4920 *
PAN, CHUNGEN ET AL.: "Combinations of the First and Next Generations of Human Immunodeficiency Virus (HIV) Fusion Inhibitors Exhibit a Highly Potent Synergistic Effect against Enfuvirtide-Sensitive and -Resistant HIV Type 1 Strains.", JOURNAL OF VIROLOGY., vol. 83, no. 16, August 2009 (2009-08-01), pages 7862 - 7872 *
QI, ZHI ET AL.: "Rationally Designed Anti-HIV Peptides Containing Multifunctional Domains as Molecule Probes for Studying the Mechanisms of Action of the First and Second Generation HIV Fusion Inhibitors.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 283, no. 44, 31 October 2008 (2008-10-31), pages 30376 - 30384 *
SHI, W. ET AL.: "Research and Development of HIV Fusion Inhibitor", CHINESE JOURNAL OF NEW DRUGS, vol. 15, no. 17, September 2006 (2006-09-01), pages 1429 - 1436 *
SHI, W. ET AL.: "Research Status and Development Trend of HIV-1 Fusion Inhibitor", JOURNAL OF CHINESE PHARMACEUTICAL SCIENCES, vol. 45, no. 2, February 2010 (2010-02-01), pages 184 - 193 *
SHI, WEIGUO ET AL.: "Novel Anti-HIV Peptides Containing Multiple Copies of Artificially Designed Heptad Repeat Motifs.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS., vol. 374, no. 4, 3 October 2008 (2008-10-03), pages 767 - 772 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019223642A1 (fr) * 2018-05-23 2019-11-28 中国人民解放军军事科学院军事医学研究院 Polypeptide antiviral, composition pharmaceutique et utilisation associées

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