Probing the Action of Screened Anticancer Triazole–Tetrazole Derivatives Against COVID-19 Using Molecular Docking and DFT Investigations

Abstract

Drugs are continuously being evaluated for novel therapeutic uses. The purpose of this work was to screen anticancer triazole/tetrazole derivatives for effectiveness against the SARS-CoV-2 main protease (Mpro). First, the chemical structures’ activity was derived from conceptual quantum chemical calculations. According to molecular docking analysis, the compounds scored good interactions against SAR-COV-2's Mpro, with binding energies extending from −8.21 to −8.97 kcal/mol. The docked complexes included various bindings with His41 and Cys145, both catalytic residues responsible for cleavage of the SARS-CoV-2 Mpro. Among the 4 studied compounds, TD3 exhibited the highest affinity by achieving the most stable binding energy and lowest value for the inhibition constant. Most striking was that TD3 not only formed strong bonds with the catalytic residues His41 and Cys145, but also captured the residues of the catalytic loop (Cys44 to Pro52), which flank the catalytic dyads in Mpro's active site. As a result, the studied triazole/tetrazole derivatives, notably TD3, must be reviewed as potent drugs that could be repurposed for SARS-CoV-2 treatment.