Hydration Structure and Dynamics of the Favipiravir Antiviral Drug: A Molecular Modelling Approach

Abstract

Abstract The hydration structure of the Favipiravir antiviral drug, at infinite dilution in water, was investigated by employing a systematic molecular modelling approach. An effective interaction potential model was employed for Favipiravir, using the intramolecular geometry and charge distribution from quantum chemical calculations performed in the present treatment and adopting well-established Lennard-Jones parameters. The hydration structure and related dynamics were further investigated by means of classical molecular dynamics simulations. These calculations have revealed the existence of different types of hydrogen bonds between Favipiravir and the surrounding water molecules, with continuous lifetimes in the sub picosecond range and intermittent lifetimes in the range of 0.8–5.4 ps. The self-diffusion coefficient of Favipiravir at 298.15 K was found to be three times lower than the value obtained for water in solution, while comparable to the values measured for other common painkillers, anti-inflammatory drugs, antibiotics and corticosteroids for asthma treatment. It was also revealed that the rotational motions of Favipiravir are more retarded in comparison with water and this is reflected in the calculated reorientational correlation times of specific intramolecular vectors. The results obtained could be useful for further pharmacokinetic and computer-aided docking studies to evaluate the efficiency of this antiviral drug.