To elucidate the modes through which Zn6S6 and Zn6O6 interact with SARS-CoV-2, the crystal structure of the main protease (M pro ) of the virus in the complex with 6-(ethylamino)pyridine-3-carbonitrile was downloaded . The main variant of SARS-CoV-2 M pro (R60C) was also prepared to investigate the interaction modes of these clusters in native and mutant enzymes. According to Khan et al. , the R60C mutation in M pro affects protein stability, thereby affecting the binding of ligands in the active site. The hydrogen bond network analysis demonstrated that the R60C mutation causes a disturbance in the interactions with the ligand as well as other surrounding active site M pro residues. The authors noticed a large fluctuation in the hydrogen-bond network of the mutant M pro . Also, the Zn6S6 and Zn6O6