In Silico Investigation on the Binding of Organoselenium Compounds with Target Proteins of SARS-CoV-2 Infection Cycle

Since the outbreak of coronavirus disease 2019 (COVID-19), researchers have been investigating the potential of several low molecular weight compounds from both natural and synthetic origins to design anti-viral drugs against SARS-CoV-2. On similar lines, the present study is aimed to evaluate different organoselenium compounds and their sulfur analogues by using a molecular docking approach to inhibit viral proteins like spike (S) glycoprotein (PDB code: 6VXX) and main protease (M^pro) (PDB code: 6LU7) and a host protein, Furin (PDB code: 5MIM), all of which are known to play significant role in SARS-CoV-2 infection cycle. The organoselenium compounds used in the study are mostly in-house synthesized including simple selenium containing amino acids and their derivatives and selenopyridines and their derivatives. The docking calculations were performed using AutoDock Vina. In brief, organoselenium compounds showed stronger binding with the target proteins as compared to their sulfur analogue, except oxidized glutathione. Notably, the most potent docked ligands shared a common structural feature of aromatic amide moieties connected by diselenide bridge. Further, the compounds ebselen diselenide (EbSeSeEb) and nicotinamide diselenide (NictSeSeNict) exhibited the highest binding affinity (in range of ~10⁵ µM^-1) to all the above three proteins. Thus, the present investigation highlights the influence of structure and substitution of organoselenium compound on their binding with the SARS-CoV-2 proteins and proposes NictSeSeNict as a candidate molecule for evaluating anti-viral activity against SARS-CoV-2 using preclinical biological models.