An in silico design of antivirus nickel (II) complexes as therapeutic drug candidates

A series of novel nickel (II) complexes [Ni(L1)](1), [Ni(L2)](2), [Ni(L3)](3) and [Ni(L4)](4) of salen-type Schiff base ligands (L1H2-L4H2), have been designed and synthesized, and their interaction with SARS-CoV-2 for COVID-19 and HIV virus were studied by molecular docking methods for possible therapeutic drug candidates as anti-COVID-19 and anti-HIV agents. The salen-type Schiff base ligands were condensation products of ethylene diamine with related aldehydes (3,5-Dichlorosalicylaldehyde, 5-Bromo-3-methoxy-2-hydroxy-benzaldehyde, 3,5-Diiodosalicylaldehyde, 3,5-Dinitrosalicylaldehyde). They were coordinated to metal ions through the tetradentate-N2O2 donor atoms. The newly synthesized complexes were fully characterized by different spectroscopic and physicochemical methods. The molecular and electronic structures of the complexes are studied by DFT based quantum chemical calculations. Additionally, inspired from recent developments to find inhibitors of the SARS-CoV-2 main protease, molecular docking studies are performed on the complexes to predict the binding mode and interactions between the ligands and the main protease of the SARS-CoV-2 (PDB ID: 7O46) for COVID-19. Also the binding potential of the nickel(II) complexes with HIV virus (PDB ID: 1UUI) are studied using in-silico molecular docking approach. The X-ray crystallographic structure of the main protease of the SARS-CoV-2 and HIV virus are retrieved from the protein data bank and used as receptor proteins. The molecular docking calculations of the nickel (II) complexes (1)-(4) with SARS-CoV-2 (PDB ID: 7O46) virus revealed the higher binding energy (-9.6 to-6.9 kcal/mol) than that of HIV virus (-9.3 to-6.7 kcal/mol) as well as docking results of chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) as anti-SARS-CoV-2 drugs. Overall, in-silico molecular docking study offers the potential role of the nickel (II) complexes as anti-COVID-19 and anti-HIV agents.