Characterization of the tautomeric equilibrium of molnupiravir, an antiviral for the treatment of COVID-19

A combined experimental NMR and DFT computational analysis of molnupiravir, an orally dosed antiviral effective for treatment of patients with COVID-19, determined that the molecule primarily exists as an oxime tautomer both in solution and in solid state. Both Z and E oxime stereoisomers were observed in various solvents, with Z being the major form, consistent with the DFT calculations. An amine form was not detected directly, but the results strongly suggest that it exists as the transient intermediate responsible for the interconversion of E and Z oxime isomers observed in solution. The Z oxime form was identified to be the predominant form in the solid state.