An in silico study on inhibitability of Baloxavir marboxil, Baricitinib, Galidesivir, Nitazoxanide, and Oseltamivir against SARS-CoV-2

ABSTRACT

Baloxavir marboxil (D1), Baricitinib (D2), Galidesivir (D3), Nitazoxanide (D4), and Oseltamivir (D5) are well-known performing broad-spectrum activity against a variety of viruses, thus holding high potentiality towards SARS-CoV-2. Quantum properties were examined using density functional theory (DFT). The inhibitability of the drugs towards Angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 main protease (6LU7) was evaluated by molecular docking simulation, while their bio-compatibility was justified by physicochemical properties obtained from QSARIS-based analysis in reference to Lipinski's rule of five. Quantum analysis suggests that the compounds are highly favourable for intermolecular interaction towards protein structures. Given ligand-ACE2 systems, the inhibitory effectiveness follows the order D3-ACE2?>?D4-ACE2?>?D2-ACE2?>?D5-ACE2?>?D1-ACE2;and the corresponding order for ligand-6LU7 systems is D2-6LU7?>?D4-6LU7?>?D3-6LU7?>?D5-6LU7?>?D1-6LU7. Galidesivir is predicted as the most effective inhibitor towards both targeted protein structures (DSaverage -13.1 kcal.mol-1) and the most bio-compatible molecule (Mass 264.9 amu;LogP -0.9;Polarisability 26.8 Å3). The theoretical screening suggests all drugs, especially Galidesivir (D3), promising for treatment of SARS-CoV-2 infection and encourages in-related clinical trials.