The novel coronavirus was declared a global pandemic after its devastating effect was felt in most countries across the world. This study therefore highlights casticin as a potential allosteric modulator of the SARS-CoV-2 main protease, which could be optimized and developed into a potential lead compound for anti-SARS-CoV-2 chemotherapy. Molecular dynamic simulations revealed that binding of casticin at the distal site interferes with the proper orientation of the peptide substrate in the oxyanion hole of the active site, and this could lead to a halt or decrease in catalytic activity. M pro only, M pro-peptide (binary) and M pro-peptide-casticin (ternary) complexes were subjected to molecular dynamics simulations for 50 ns to investigate the modulatory activity of casticin binding on M pro. This site, characterized as a distal site, has been shown to have an interdependent dynamic effect with the active site region. Molecular docking revealed a strong interaction between casticin, an antiviral flavonoid, and M pro at a site distant from the active site. In this study, the ability of antiviral natural products to inhibit M Pro in an allosteric fashion was explored with in silico techniques. Allosteric inhibition can potentially serve as an effective strategy for alleviating these limitations. Most efforts aimed at inhibiting M Pro activity have been channeled into competitive inhibition at the active site, but this strategy will require a high inhibitor concentration and impressive inhibitor-M Pro binding affinity. Inhibition of the main protease (M pro) of SARS-CoV-2 has been suggested to be vital in shutting down viral replication in a host.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |