Method for screening small molecule peptidomimetic inhibitor and application of small molecule peptidomimetic inhibitor

An inhibitor, small molecule technology, applied in the field of medicine, can solve the problem of lack of specific antiviral drugs

Inactive Publication Date: 2020-10-23
JINHUA VOCATIONAL TECH COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] For new coronary pneumonia, there is still a lack of specific antiviral drugs, and the selection of therapeutic drugs is mostly based on the treatment experience of SARS or other influenza viruses. The research and development of safe, efficient and economical antiviral drugs is still imminent

Method used

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  • Method for screening small molecule peptidomimetic inhibitor and application of small molecule peptidomimetic inhibitor
  • Method for screening small molecule peptidomimetic inhibitor and application of small molecule peptidomimetic inhibitor
  • Method for screening small molecule peptidomimetic inhibitor and application of small molecule peptidomimetic inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1 Processing of SARS-Cov-2-RdRp protein crystal structure

[0039] The three-dimensional crystal structure of RdRp protein can be searched and downloaded from the PDB data, the PDB code is 7BV2, and the resolution of the crystal structure is It is the nsp12-nsp7-nsp8 complex, including the RNA chain and the phosphate form of remdesivir structure. Use the "pretein preparation wizard" of Maestro software to correct the chemical bond sequence of the 7BV2 structure, add hydrogen, deal with metal ions, fill in missing atoms and amino acid residues, delete redundant molecules, etc., and then perform protein preparation under OPLS force field conditions Energy optimization, and finally use it as an acceptor for molecular docking.

Embodiment 2

[0040] Example 2 drug binding site

[0041] 7BV2 is a complex complex composed of nsp12-nsp7-nsp8 complex and template primer RNA, and only nsp12 peptide chain is retained when processing protein. In order to detect potential binding sites of nsp12, this example uses the FTmap (http: / / ftmap.bu.edu / login.php) online platform and the site map section in Maestro. The results show that there are two main binding sites, one is the binding site of remdesivir metabolic active substances, and the key amino acid residues that make up the pocket are LYS545, SER682, ASP623, THR687, SER759, ASP760 and ASN691, etc.; The binding site (potential allosteric site) next to the site, the key amino acid residues that make up the pocket are PHE165, PRO169, ASP170, LEU172, ARG173, THR246, LEU247, ARG249, TYR265, THR319, PRO323, THR324, ARG349 , LEU389, ASP390, LYS391, THR393, THR394, PHE396, ARG457, TYR458, LEU460, PRO461, THR462 and PRO677, etc. The positions of the two binding sites are as im...

Embodiment 3

[0042] The selection of embodiment 3 compound library

[0043] Recent studies have shown that the anti-SARS-CoV-2 virus is basically a peptidomimetic compound. In this example, a compound library based on bacterial and fungal metabolites was established with the help of the compound library provided by npatla, which contains a large number of peptide-like compounds. Molecular docking analysis of RNA-dependent RNA polymerase (RdRp) inhibitors was carried out by means of computer-aided drug design (CADD) method.

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Abstract

The invention discloses a method for screening a small molecular peptidomimetic inhibitor based on a COVID-19RdRp allosteric site and an application of the small molecular peptidomimetic inhibitor. The screening method specifically comprises the steps: (1) treating an SARS-Cov-2-RdRp protein crystal structure; 2) determining a drug binding site; 3) selecting a compound library; 4) treating a compound structure; 5) carrying out molecular docking; and 6) result obtaining and analysis. The advantages of virtual screening are brought into full play, the blindness of experiments is reduced, the success rate of inhibitor drugs is effectively increased, and manpower, material resources and financial resources are saved; the invention further provides the application of the inhibitor obtained through screening in preparation of drugs for treating novel coronavirus.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a method for screening small molecule peptidomimetic inhibitors based on the allosteric site of COVID-19RdRp and its application. Background technique [0002] Coronavirus (Coronabiridae / coronavirus, CoV) is a class of pathogenic microorganisms that exist widely and have great potential threats to humans and livestock. The virus was first discovered in infected tissues of chickens in 1937, with crown-like spike-like protrusions on the surface, and was finally identified as a new species and thus named coronavirus. The main route of transmission of the new coronavirus SARS-CoV-2 is respiratory droplet transmission and contact infection. There are a large number of antiviral drugs on the market, but there is no specific treatment drug for SARS-CoV and SARS-CoV-2, so the market There is an urgent need for one or more vaccines or effective treatments against these viruses. [0003...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C40B30/04G16B20/30
CPCC40B30/04G16B20/30
Inventor 毛辉胡献跃刘振香
Owner JINHUA VOCATIONAL TECH COLLEGE
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