SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, represents a new strain of Coronaviridae . In the closing 2019 to early 2020 months, the virus caused a global pandemic of COVID-19 disease. We performed a virtual screening study in order to identify potential inhibitors of the SARS-CoV-2 main viral protease (3CL pro or M pro ). For this purpose, we developed a novel approach using ensemble docking high-throughput virtual screening directly coupled with subsequent Linear Interaction Energy (LIE) calculations to maximize the conformational space sampling and to assess the binding affinity of identified inhibitors. A large database of small commercial compounds was prepared, and top-scoring hits were identified with two compounds singled out, namely 1-[(R)-2-(1,3-benzimidazol-2-yl)-1-pyrrolidinyl]-2-(4-methyl-1,4-diazepan-1-yl)-1-ethanone and [({(S)-1-[(1H-indol-2-yl)methyl]-3-pyrrolidinyl}methyl)amino](5-methyl-2H-pyrazol-3-yl)formaldehyde. Moreover, we obtained a favorable binding free energy of the identified compounds, and using contact analysis we confirmed their stable binding modes in the 3CL pro active site. These compounds will facilitate further 3CL pro inhibitor design.
【저자키워드】 COVID-19, SARS-CoV-2, Virtual screening, inhibitors, 3C-like protease, MPro, in silico drug design, 3CLpro, free-energy calculations, 【초록키워드】 coronavirus, 3CL pro, docking, protease, virus, binding free energy, database, COVID-19 disease, global pandemic, inhibitor, Coronaviridae, compounds, Analysis, Contact, energy, acute respiratory syndrome, Compound, M pro, new strain, approach, identify, performed, caused, subsequent, facilitate, conformational, the binding affinity, binding mode, the SARS-CoV-2, 【제목키워드】 3CL pro, identification, energy, calculation,