A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHEPh-AgCl and (NHEPh-AgCl)(2)with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (NHE-Ag) and bis-silver-tetrylene complexes (NHE-Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC-AgandNHC-Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligandNHCbonds in a head-on configuration with AgCl and (AgCl)(2), whereas, the otherNHE(E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order ofNHC-Ag>NHSi-Ag>NHGe-AgandNHSi-Ag-bis>NHGe-Ag-bis>NHC-Ag-bis. The natural bond orbital analysis implies that the [NHEPh -> AgCl] and [(NHEPh)(2)->(AgCl)(2)] donations are derived mainly from the sigma- and pi-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbeneNHC-Ag, bis-silver-carbeneNHC-Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from -17.5 to -16.5 kcal mol(-1)and -16.9 to -16.6 kcal mol(-1), respectively. The root-mean-square deviation values were recorded to be less than 2 angstrom in all the calculated systems. Thus, the present study suggests that silver-carbeneNHC-Agand bis-silver-carbeneNHC-Ag-biscomplexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.