Antagonistic polypeptide and application thereof in preparation of novel coronavirus resistant drugs

A coronavirus, antagonistic technology, applied in the field of biopharmaceuticals, can solve problems such as poor safety, poor efficacy, and lack of drugs

Active Publication Date: 2020-12-15
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention solves the technical problems of lack of drugs for treating new coronavirus and SARS virus in the prior art, poor eff

Method used

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  • Antagonistic polypeptide and application thereof in preparation of novel coronavirus resistant drugs
  • Antagonistic polypeptide and application thereof in preparation of novel coronavirus resistant drugs
  • Antagonistic polypeptide and application thereof in preparation of novel coronavirus resistant drugs

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0037] Example 1

[0038] KIM1 LEU54, PHE55, GLN58 (binding pockets 1), TRP112, PHE113 (joint pocket 2) can be combined with SARS-COV-2 and SARS-COV.

[0039] Get the crystal structure of KIM1 (PDB ID: 5DZO), SARS-COV-2-RBD (PDBID: 6M0J), and SARS-COV-2-RBD (PDBID: 2AJF) from the Protein Data Bank database, import Z-Dock programs, find Potential binding pattern. Dynamic analysis is performed for a preferred binding model. The 50NS kinetics were submitted to study the kinetic parameters of KIM1 and SARS-COV-2-RBD protein complex, and analyzed the obtained MM-GBSA binding energy parameters. The results of molecular simulation dock show that KIM1 LEU 54, PHE55, GLN58 (binding pocket 1), TRP 112, PHE113 (binding pocket 2) can be combined with SARS-COV-2's PHE338, VAL367, SER371, PHE374 and TRP436, accumulated binding Can analyze -35.64kcal / mol; and analyze the obtained MM-GBSA binding energy parameters. The results of molecular simulation docking showed that KIM1 LEU54, PHE55, GLN58...

Example Embodiment

[0047] Example 2

[0048] The antagonistic peptide 1 of the present invention has strong affinity on the SARS-COV-2-thorn protein receptor binding domain (RBD).

[0049] The antagonistic peptide 1 is modeled by homologous modeling, and is coupled to the SARS-COV-2-Tensin receptor binding domain (RBD), and the combined energy parameters are analyzed. The results showed that antagonistic peptide 1 and SARS-COV-2-mining protein receptor binding domain (RBD) binding can be -6.65 kcal / mol, indicating antagonism peptide 1 on SARS-COV-2-thorn protein receptor binding domain (RBD) has strong affinity.

Example Embodiment

[0050] Example 3

[0051] The antagonistic peptide 1 of the present invention has no obvious cytotoxicity, and can inhibit the syndrome and cytotoxicity of SARS-COV-2-prolinine receptor binding domain (RBD).

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Abstract

The invention relates to an antagonistic polypeptide and application thereof in preparation of novel coronavirus resistant drugs, and belongs to the technical field of biopharmacy. The antagonistic polypeptide contains an amino acid sequence shown as SEQ ID NO: 1 from the N terminal to the C terminal, or the antagonistic polypeptide contains an amino acid sequence shown as SEQ ID NO: 1 from the Nterminal to the C terminal, and the N terminal or the C terminal of the amino acid sequence shown as SEQ ID NO: 1 is connected with an amino acid sequence shown as SEQ ID NO: 2 from the N terminal tothe C terminal; and the antagonistic polypeptide can be competitively combined with an endocytosis receptor and a receptor binding domain of a novel coronavirus or SARS virus. The antagonistic polypeptide has a strong antagonistic effect on SARS-CoV/SARS-CoV-2, can effectively block SARS-CoV/SARS-CoV-2 endocytosis, and inhibits SARS-CoV/SARS-CoV-2 induced renal epithelial cell death. The antagonistic polypeptide can be used for preparing drugs for antagonizing SARS-CoV/SARS-CoV-2, and can be applied to prevention and treatment of new coronavirus and SARS virus infection and renal complicationsthereof.

Description

technical field [0001] The present invention belongs to the field of biopharmaceuticals, and more specifically, relates to an antagonistic polypeptide and its application for preparing anti-new coronavirus drugs, especially to an antagonistic polypeptide of novel coronavirus and SARS virus spike protein, which is used for preparing anti-new coronavirus And the application of SARS virus medicine. Background technique [0002] Novel coronavirus (SARS-CoV-2) infection has symptoms such as fever, cough, shortness of breath, and dyspnea, and can lead to pneumonia, kidney damage, severe acute respiratory syndrome, organ failure, and even death. [0003] At present, angiotensin-converting enzyme 2 (ACE2) is considered to be the main receptor for the new coronavirus SARS-CoV-2 and SARS-CoV to invade host cells. Membrane proteins such as ACE2 can interact with SARS-CoV-2- / SARS- The CoV spike protein receptor domain (RBD) binds to mediate viral entry, but blockade of ACE2 can lead to...

Claims

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Application Information

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IPC IPC(8): C07K7/08A61K38/10A61P31/14
CPCA61K38/00A61P31/14C07K7/08
Inventor 黄昆杨晨陈红沈子威
Owner HUAZHONG UNIV OF SCI & TECH
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