Molecular Docking Analysis of SARS-CoV-2 Inhibitor N3 (6LU7) against Selected Flavonoids and Vitamins

Background: Coronavirus is a zoonotic disease and transmits between animals and humans. The disease known as COVID-19 (SARS-CoV-2) has become a pandemic since its outbreak. In addition to vaccines, a combination of antiretroviral agents, chloroquine derivatives, and vitamins are being used to treat SARS-CoV-2.

Method: We performed molecular docking analysis of SARS-CoV-2 inhibitor N3 (6LU7) using a series of flavonoid derivatives and vitamins. The X-ray crystallographic 3D structures of COVID-19 main protease in complex with an inhibitor N3 (PDB code: 6LU7, resolution 2.16 Å complexed with a selective substance) were downloaded from the online Protein Data Bank. The structures of the ligands and protein were constructed using ChemDrawUltra 8.0. The docking process, interactions, and binding of ligands were visualized using the software Molegro Virtual Dockings (MVD). The physicochemical and toxicity characteristics of tested flavonoid derivatives and vitamins were determined using Swiss-ADME and pkCSM online software. We found that molecular docking scores were between -64.42 and –172.00 Kcal/mol. The H-bonding and steric interactions were compared with other flavonoid derivatives. The ADMET parameters suggested that compounds 4, 68, 90, 92, and 94 have a higher GI rate.

Results: Our results also indicated that compound 78 was more potent and had higher skin permeation than other flavonoid derivatives. The study showed that the compounds 5, 28, 74, 78, and folic acid fitted well in the active site of COVID-19 inhibitor N3 (6LU7) and interacted with the residues in the active site, which are essential for their biological activity.

Conclusion: Therefore, compounds 5, 28, 74, and 78 and folic acid can be a COVID-19 inhibitor N3 (6LU7) and might be used in the treatment of COVID-19 infection.