In silico study of potential antiviral activity of copper(II) complexes with non–steroidal anti–inflammatory drugs on various SARS–CoV–2 target proteins

Abstract

In silico molecular docking studies, in vitro toxicity and in silico predictions on the biological activity profile, pharmacokinetic properties, drug–likeness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) physicochemical pharmacokinetic data, and target proteins and toxicity predictions were performed on six copper(II) complexes with the non–steroidal anti–inflammatory drugs ibuprofen, loxoprofen, fenoprofen and clonixin as ligands, in order to investigate the ability of these complexes to interact with the key therapeutic target proteins of SARS–CoV–2 (Severe Acute Respiratory Syndrome Coronavirus 2) 3C–like cysteine main protease (3CLpro/Mpro), viral papain–like protease (PLpro), RNA–dependent RNA polymerase (RdRp), and non–structural proteins (Nsps) Nsp16–Nsp10 2′–O–methyltransferase complex, and their capacity to act as antiviral agents, contributing thus to understanding the role they can play in the context of coronavirus 2019 (COVID–19) pandemic. Cytotoxic activity against five human cancer and normal cell lines were also evaluated.