Compound for inhibiting combination of novel coronavirus spike protein and ACE2 and application thereof

Abstract

The invention discloses a compound for inhibiting combination of novel coronavirus spike protein and ACE2, the compound is a compound A or a compound B, the IC50 value of the compound A for inhibiting ACE2 is less than 50 [mu] M, and the IC50 value of the compound B for inhibiting ACE2 is less than 1 [mu] M; the compound A is dipeptide or tripeptide, hydrophobic amino acid residues exist at the C end of the compound A, and the hydrophobic amino acid residues comprise any one of residues of proline, tyrosine, phenylalanine and tryptophan; the compound B is a pril drug containing the structure of the compound A, and the pril drug comprises but is not limited to captopril, enalapril, lisinopril, fosinopril, perindopril, benazepril and eplerenone; the compound can be combined with an RBD region of a novel coronavirus S protein, competitively blocks combination of the RBD region and an ACE2 receptor, and has a positive effect on prevention of the novel coronavirus SARS-CoV-2.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a compound for inhibiting the combination of a novel coronavirus spike protein and ACE2 and an application thereof. Background technique [0002] The spike protein of the new coronavirus helps the virus to recognize and enter target cells. A number of research groups have shown using the SARS-CoV-2 Spike protein to bind to ACE2 via its receptor binding domain (RBD). The receptor ACE2 is a dipeptide carboxypeptidase on the outer skin of the cell. The enzyme is characterized by being able to fuse with the cell, thereby carrying the virus into the cell. After the virus enters the cell, it can infect human cells through expression. Therefore, one of the key ways to treat viral infections in medicine is to block the entry of the virus into cells. Therefore, inhibiting the interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is currently consid...

AI Technical Summary

Problems solved by technology

[0003] At present, there are no drugs specifically for the prevention and treatment of the new coronavirus, but the effect of peptide compounds on inhibiting the interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor has been reported, such as the application publication number CN111825750A of China The patent application designed a series of protein peptides based on the amino acid structure of RBD, and modified the amino acid structure of the peptides, and tested that these peptides can block the combination of RBD and ACE2 through molecular, cell and animal levels Function; the Chinese patent with the authorized announcement number CN 111349150B designed a specific binding polypeptide according to the HR2 region of the new coronavirus S protein, which can block the fusion of the virus and the cell, and can effectively prevent the infection of the virus; the authorized announcement number is The Chinese patent of CN 112079901B synthesized a class of antagonistic polypeptides based on the structure of the RBD region of the S protein of the new coronavirus virus, which can compete with the RBD and bind to the receptor ACE2, thereby preventing the new coronavirus from entering cells and playing a role in kidney epithelial cells. Protective effects

However, the peptide compounds synthesized above still have the problems of large workload, small quantity, too long chain length, and low absorption and utilization rate to the human body.

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