Development of antiviral drugs based on inhibitors of the SARS-COV-2 main protease

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database Voronezh State University to find inhibitors SARS-CoV-2 main protease, an important enzyme coronavirus responsible COVID-19 pandemic. Using SOL program more than 42000 3D molecular structures were docked into active site 1000 ligands with most negative values score selected further processing. For all these top ligands, protein-ligand binding enthalpy has calculated using PM7 semiempirical method COSMO implicit solvent model. 20 scores enthalpies experimental testing. The latter made by measurements inhibitory activity against protease suppression replication in a cell culture. \of was determined synthetic fluorescently labeled peptide substrate including proteolysis protease. antiviral tested virus Vero Eight showed submicromolar micromolar ranges IC50 values. Three suppressed culture at range EC50 had low cytotoxicity. found chemically diverse can be optimization order obtain leader compound, basis new direct-acting drugs coronavirus.