Theoretical studies of the rotational and tautomeric states, electronic and spectroscopic properties of favipiravir and its structural analogues: a potential drug for the treatment of COVID-19

Abstract

ABSTRACT Favipiravir is a broad spectrum antiviral drug that has shown activity against many viruses. Sequel to the recent outbreak of COVID-19, favipiravir is investigated as one of the potential drugs for the treatment of SARS-CoV-2. To augment these efforts, this article reports the rotational isomers, tautomeric states, electronic and spectral properties of favipiravir and its five analogues (Cl, Br, H, CN and CH3) using quantum chemcial code. The enol forms are more stable and the calculated keto–enol relative energies are in the range of 7.86–10.72 kcal/mol in the gas phase and 1.07–3.46 kcal/mol in the solution phase. The relative stabilization of the more polar keto structure in water environment leads to a significant reduction in keto–enol relative energy by 68% for T705, 71% for T705–Cl and T705–Br, 86% for T1105 (H), 88% for T705–CN and 80% for T705–CH3. The density functional theory and time-dependent density functional theory with the 6-311++G(d,p) basis set were used in the computation. The theoretical results were successfully compared with available experimental and theoretical data.