Allosteric Modulation of the Main Protease (MPro) of SARS-CoV-2 by Casticin—Insights from Molecular Dynamics Simulations

Inhibition of the main protease (Mpro) SARS-CoV-2 has been suggested to be vital in shutting down viral replication a host. Most efforts aimed at inhibiting MPro activity have channeled into competitive inhibition active site, but this strategy will require high inhibitor concentration and impressive inhibitor-MPro binding affinity. Allosteric can potentially serve as an effective for alleviating these limitations. In study, ability antiviral natural products inhibit allosteric fashion was explored with silico techniques. Molecular docking revealed strong interaction between casticin, flavonoid, Mpro site distant from site. This characterized distal shown interdependent dynamic effect region. only, Mpro-peptide (binary) Mpro-peptide-casticin (ternary) complexes were subjected molecular dynamics simulations 50 ns investigate modulatory casticin on Mpro. that interferes proper orientation peptide substrate oxyanion hole could lead halt or decrease catalytic activity. study therefore highlights potential modulator protease, which optimized developed compound anti-SARS-CoV-2 chemotherapy.