In this work, we report in-depth computational studies of three plausible tautomeric forms, generated through the migration of two acidic protons of the N4-hydroxylcytosine fragment, of molnupiravir, which is emerging as an efficient drug to treat COVID-19. The DFT calculations were performed to verify the structure of these tautomers, as well as their electronic and optical properties. Molecular docking was applied to examine the influence of the structures of the keto-oxime, keto-hydroxylamine and hydroxyl-oxime tautomers on a series of the SARS-CoV-2 proteins. These tautomers exhibited the best affinity behavior (-9.90, -7.90, and -9.30 kcal/mol, respectively) towards RdRp-RTR and Nonstructural protein 3 (nsp3_range 207-379-MES).
Keywords: COVID-19; DFT; SARS-CoV-2; computational study; molecular docking; molnupiravir; virus.