Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors: <i>In Silico</i> Modeling and <i>In Vitro</i> Screening

Currently the entire human population is in midst of a global pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2). This highly pathogenic virus has to date >71 million infections and >1.6 deaths >180 countries. Several vaccines drugs are being studied as possible treatments or prophylactics this viral infection. M3CLpro (coronavirus main cysteine protease) promising drug target it significant role replication. Here we use X-ray crystal structure complex with boceprevir study dynamic changes protease upon ligand binding. The binding free energy was calculated for water molecules at different locations site, molecular dynamics (MD) simulations were carried out M3CLpro/boceprevir complex, thoroughly understand chemical environment site. HCV NS3/4a inhibitors tested vitro against M3CLpro. Specifically, asunaprevir, narlaprevir, paritaprevir, simeprevir, telaprevir all showed inhibitory effects on Molecular docking MD then performed investigate these ligands provide insights into Our findings observations offered help guide design potent aid coping COVID-19 pandemic.