Screening method of small-molecule inhibitor of COVID-19 spinous process protein, active molecule screened by screening method and application of small-molecule inhibitor

Abstract

The invention discloses a screening method of a COVID-19 spike protein inhibitor, an active molecule screened by the screening method and application of the inhibitor. The screening method comprises the following steps of: acquiring a three-dimensional structure of a cocrystal of COVID-19 spike protein and human angiotensin converting enzyme 2 from a database; acquiring active molecules and derivatives thereof of traditional Chinese medicinal materials from a traditional Chinese medicinal material active component database, and constructing a compound library of small molecules; and establishing a pharmacophore model, taking the pharmacophore model as a query formula, screening based on the matching degree value, and selecting a small molecule compound with the normalized matching value greater than 0.35. The effective S protein small-molecule inhibitor can be rapidly and effectively screened out according to the link that the novel coronavirus invades the S protein of the human cells to be combined with the human ACE2, and the screened-out inhibitor is definite in effect and has an application prospect in prevention or / and treatment of novel coronavirus pneumonia.

Description

technical field [0001] The invention belongs to the field of medicine and biotechnology, and in particular relates to a screening method for a COVID-19 spike protein inhibitor, an active molecule screened by it, and an application thereof. Background technique [0002] Human coronavirus spike protein (COVID-19Spike protein, S protein) is a class of virus fusion protein, S protein binding host receptor is a key step in virus infection of cells, can be used as the target of drugs to inhibit human coronavirus [Structural and functional properties of SARS-CoV-2 spikeprotein: potential antivirus drug development for COVID-19, Acta Pharmacologica Sinica, 2020]. In April this year, a team of Chinese scientists worked together to analyze the crystal structure (PDB ID: 6LZG) of the complex between the S protein of COVID-19 and angiotensin-converting enzyme 2 (ACE2) on the surface of human cells. Human novel coronavirus COVID-19 belongs to betacoronavirus, and the S1 subunit of its S...

AI Technical Summary

Problems solved by technology

At present, most studies on this target are host neutralizing antibodies and vaccine design, and reports on small molecule inhibitors are relatively rare

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