Search

CN-121987762-A - Novel coronavirus membrane fusion inhibitor and preparation method and application thereof

CN121987762ACN 121987762 ACN121987762 ACN 121987762ACN-121987762-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a novel coronavirus membrane fusion inhibitor, and a preparation method and application thereof. The polypeptide comprises an amino acid sequence shown as SEQ ID NO.1 or derivative peptide (the derivative peptide shown as SEQ ID NO. 2-20), and is designed by implementing salt bridge mutation on HR2 sequence based on the conserved characteristic of a target point of an HR1 region of an S2 protein S2 of SARS-CoV-2S. Through in vitro 5HB interaction experiments and eukaryotic cell pseudovirus model verification, the polypeptide can interfere the normal function of virus 6HB through combining HR1, and effectively inhibit the fusion and infection process of virus membranes. The polypeptide has short and small sequence, is not easy to degrade, is convenient to modify and optimize, has low preparation cost, has good inhibition effect on SARS-CoV-2 and mutant strains and potential SARS related coronaviruses which are still popular at present, and provides important theoretical basis and medicine reserve for the research and development of anti-coronavirus medicines.

Inventors

  • GAO ZHIZENG
  • GUAN ZHIFENG
  • CAO LIU
  • ZENG QIANG
  • XIONG LONGWEI
  • CHEN LITONG
  • Zhong Cuishan
  • Ji Yanxi

Assignees

  • 中山大学

Dates

Publication Date
20260508
Application Date
20260206

Claims (10)

  1. 1. The application of the polypeptide in preparing a medicament for inhibiting coronavirus and/or preventing and treating diseases caused by coronavirus is characterized in that the polypeptide comprises at least one of the polypeptide shown in SEQ ID NO.1 or a derivative polypeptide thereof, and the derivative polypeptide of the polypeptide shown in SEQ ID NO.1 is shown in SEQ ID NO. 2-20.
  2. 2. The application of the polypeptide in preparing the coronavirus membrane fusion inhibitor is characterized in that the polypeptide comprises at least one of the polypeptide shown in SEQ ID NO.1 or a derivative polypeptide thereof, and the derivative polypeptide of the polypeptide shown in SEQ ID NO.1 is shown in SEQ ID NO. 2-20.
  3. 3. The use according to claim 2, wherein the coronavirus is SARS-CoV-2.
  4. 4. The use according to claim 2, wherein the disease caused by coronavirus is a coronavirus infection.
  5. 5. The use according to claim 2, wherein the coronavirus membrane fusion inhibitor is a coronavirus five-helix protein inhibitor.
  6. 6. The polypeptide medicine with the coronavirus resisting effect is characterized by comprising at least one of polypeptides shown in SEQ ID NO.1 or derived polypeptides thereof, wherein the derived polypeptides of the polypeptides shown in SEQ ID NO.1 are shown in SEQ ID NO. 2-20.
  7. 7. The polypeptide drug having an anti-coronavirus effect of claim 6, further comprising an agent for inhibiting coronavirus or preventing and treating a disease caused by coronavirus, said agent comprising fampicvir, nelfinavir, arbidol, lopinavir, ritonavir, chloroquine phosphate, daruna Wei Huorui darunavir.
  8. 8. The polypeptide drug having an anti-coronavirus effect of claim 6, further comprising a pharmaceutically acceptable carrier.
  9. 9. The polypeptide drug with coronavirus resistance according to claim 6, wherein the dosage form of the polypeptide drug comprises tablets, capsules, dripping pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, liposomes, transdermal agents, suppositories or freeze-dried powder injection.
  10. 10. The polypeptide drug having an anti-coronavirus effect according to claim 6, wherein the administration mode of the polypeptide drug comprises injection administration, cavity administration, respiratory administration, or mucosal administration.

Description

Novel coronavirus membrane fusion inhibitor and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a novel coronavirus membrane fusion inhibitor, and a preparation method and application thereof. Background The novel coronavirus has proved to be of animal origin, and the pathogen is rapidly identified as a new coronavirus in the early epidemic stage, and is named 2019-nCoV by the world health organization for the first time. The International Commission on classification of viruses was formally designated as Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) based on the genetic sequence characteristics and taxonomic rules of the viruses. The virus has the characteristics of high transmission speed and high crowd susceptibility, can cause multisystem damage, and can cause great threat to global public health safety. In view of this, developing specific prevention and control drugs for the virus and establishing a high-efficiency transmission prevention and control system have become key issues to be overcome. Disclosure of Invention In order to overcome the defects in the prior art, the invention takes the HR1 target point of the S2 region of the S protein of the novel coronavirus (2019-nCoV) as an action site, screens out the polypeptide or the polypeptide derivative which can independently inhibit 2019-nCoV infection, and provides a potential preventive and therapeutic candidate medicament for the current epidemic 2019-nCoV and future potential outbreak SARS-like virus. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: The first aspect of the invention provides application of a polypeptide in preparing a medicament for inhibiting coronavirus and/or preventing and treating diseases caused by coronavirus, wherein the polypeptide comprises at least one of the polypeptide shown in SEQ ID NO.1 or a derivative polypeptide thereof, and the derivative polypeptide of the polypeptide shown in SEQ ID NO.1 is shown in SEQ ID NO. 2-20. The invention also provides application of the polypeptide in preparing coronavirus membrane fusion inhibitor, wherein the polypeptide comprises at least one of the polypeptide shown in SEQ ID NO.1 or a derivative polypeptide thereof, and the derivative polypeptide of the polypeptide shown in SEQ ID NO.1 is shown as SEQ ID NO. 2-20. In principle, the polypeptide also comprises an amino acid sequence which has at least 50% homology with the polypeptide shown in SEQ ID NO.1 (preferably 50%, 55%, 61%, 66%, 72%, 77%, 83%, 88%, 94% homology), or an amino acid sequence obtained by substitution and/or deletion and/or addition of at least one amino acid residue at any position in the amino acid sequence of the polypeptide shown in SEQ ID NO.1, or an amino acid sequence obtained by modification of the amino acid sequence of the polypeptide shown in SEQ ID NO. 1. The substitution and/or deletion and/or addition of at least one amino acid residue includes addition and/or deletion at any position within the peptide or protein sequence and at both ends of the sequence. Among the mutated amino acid residues, it is preferable to mutate to other amino acids having similar properties to the side chains of the original amino acid residues. Amino acids having similar side chain properties are hydrophilic amino acids (e.g., R, D, N, C, E, Q, G, H, K, S, T), hydrophobic amino acids (e.g., A, I, L, M, F, P, W, Y, V), aliphatic side chain amino acids (e.g., G, A, V, L, I, P), hydroxyl side chain amino acids (e.g., S, T, Y), sulfur atom side chain amino acids (e.g., C, M), carboxyl-and amide side chain-containing amino acids (e.g., D, N, E, Q), basic group side chain-containing amino acids (e.g., R, K, H), acidic group side chain-containing amino acids (e.g., E, D), aromatic side chain-containing amino acids (e.g., H, F, Y, W), respectively. The modification refers to conventional modification on the amino acid sequence, or attachment of a tag for detection or purification of the polypeptide or protein. The conventional modification comprises acetylation, amidation, cyclization, glycosylation, phosphorylation, alkylation, biotinylation, fluorescent group modification, polyethylene glycol PEG modification, palmitoylation modification, cholesterol modification, immobilization modification and crosslinking modification, and the tag comprises His6, GST, eGFP, eCFP, eYFP, mCherryeGFP, MBP, nusA, HA, SUMO, igG, FLAG, c-Myc and Strep-II, profinityeXact. Still further, for example, peptides are chemically modified, such as labeled Fluorescein Isothiocyanate (FITC), biotin (Biotin), polyethylene glycol modification (PEG), immobilization modification, palmitoylation modification, cholesterol modification, cross-linking modification, etc. (including but not limited to this), sequence and structure modification, such as acetylation, amidation, cyclizatio