The number of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has reached over 114,000. SARS-CoV-2 caused a pandemic in Wuhan, China, in December 2019 and is rapidly spreading globally. It has been reported that peptide-like anti-HIV-1 drugs are effective against SARS-CoV Main protease (M pro ). Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, their main proteases share many structural and functional features. Thus, these drugs are also regarded as potential drug candidates targeting SARS-CoV-2 M pro . However, the mechanism of action of SARS-CoV-2 M pro at the atomic-level is unknown. In the present study, we revealed key interactions between SARS-CoV-2 M pro and three drug candidates by performing pharmacophore modeling and 1 μs molecular dynamics (MD) simulations. His41, Gly143, and Glu166 formed interactions with the functional groups that were common among peptide-like inhibitors in all MD simulations. These interactions are important targets for potential drugs against SARS-CoV-2 M pro .
【저자키워드】 Infectious diseases, Virtual drug screening, Computational biology and bioinformatics, Drug screening, 【초록키워드】 COVID-19, SARS-CoV-2, coronavirus, pandemic, SARS-CoV, Infection, drug, protease, MD simulations, Features, target, molecular, group, mechanism of action, Interaction, Phylogenetic relationship, acute respiratory syndrome, M pro, His41, drug candidate, Glu166, Gly143, effective, Wuhan, China, caused, reported, functional, against SARS-CoV, reached, drug candidates targeting, peptide-like inhibitor, 【제목키워드】 SARS-CoV-2 main protease, inhibitor, Interaction, identification, drug candidate,