DFT, molecular docking, and ADME/Tox screening investigations of Market-Available drugs against SARS-CoV-2

Araújo, J. L.; de Sousa, L. A.; Sousa, A. O.; Bastos, R. S.; Santos, G. T.; Lage, M. R.; Stoyanov, S. R.; Passos, I. N. G.; de Azevedo, R. B.; Rocha, J. A.

A series of drugs was investigated to determine structural, electronic and pharmacological properties, as well as the molecular affinity for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The drugs were submitted to density functional theory calculations to optimize structures and predict binding preferences. The optimized geometries were used in molecular docking simulations. In the docking study, the receiver was considered rigid and the drugs flexible. The Lamarckian genetic algorithm with global search and Pseudo-Solis and Wets with local search were adopted for docking. Absorption, distribution, metabolism, excretion and toxicological properties were obtained from the Pre-ADMET online server. In this series, the antiviral atazanavir showed the potential to inhibit the main protease of SARS-CoV-2, based on the free binding energy, inhibition constant, binding interactions and its favorable pharmacological properties. Therefore, we recommend carrying out further studies with in vitro tests and subsequent clinical tests to analyze its effectiveness in the treatment of SARS-CoV-2. © 2021 Sociedade Brasileira de Química.