Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase.

摘要: Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated widespread fear, threatening global health safety. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials under way to test possible therapies. During this urgent situation, computational drug discovery methods provide an alternative tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification small molecules that specifically target viral replication apparatus has indicated highest potential towards discovery. In work, we present compounds vital proteins, including main protease, Nsp12 RNA polymerase Nsp13 helicase. An integrative virtual screening molecular dynamics simulations approach facilitated identification binding modes favourable interaction profile corresponding compounds. Moreover, structurally important site residues conserved motifs located inside active highlights relative importance ligand based on residual energy decomposition analysis. Although current study lacks experimental validation, structural information obtained from paved for design targeted inhibitors combat outbreak.