Design and synthesis of copper(II) and nickel(II) complexes as potential inhibitors against SARS-CoV-2 viral RNA binding protein and Omicron RBD protein.

Two new bis-Schiff base metal(II) complexes viz., bis{N′-[(6-methoxynaphthalen-2-yl)methylidene]-N-methylcarbamohydrazonothioato}-copper(II) complex [Cu(L)2](1) and bis{N′-[(6-methoxynaphthalen-2-yl)methylidene]-N-methylcarbamohydrazonothioato}-nickel(II) complex [Ni(L)2](2), were synthesized and designed from a bidentate-N,S donor Schiff base ligand (HL), and characterized via a single crystal X-ray diffraction (SC-XRD) study, FT-IR, UV-visible and fluorescence spectroscopy, thermal analysis and DFT calculations. Single crystal X-ray diffraction analysis established the perfect square-planar geometry around the metal(II) ions obtained by the coordination of the two N and two S atoms from the two deprotonated HL ligands. Non-covalent intermolecular interactions, which are the main features of the supramolecular assembly, were investigated via Hirshfeld surface (HSs) analysis and 2D-fingerprint plots (FPs) for both the complexes. The supramolecular architecture within the crystal packing is stabilized by C–H⋯S, C–H⋯O and N–H⋯O type hydrogen bonds for the copper(II) complex [Cu(L)2](1), while C–H⋯S, C–H⋯N and N–H⋯O connecting units stabilize the supramolecular assembly for the nickel(II) complex [Ni(L)2](2). The thermal properties of the synthesized complexes offer valuable details on the stability of the complexes. The intermolecular interaction energies have been estimated and their topologies were explored using energy framework analysis. Their interactions with calf-thymus DNA (CT-DNA) and bovine serum albumin (BSA) proteins were also evaluated using UV-visible and fluorescence spectroscopic methods. Absorption titration studies revealed that they interacted strongly with CT-DNA. To gain insight into the potential antiviral applications, we examined the molecular docking of the copper(II) complex [Cu(L)2](1) and nickel(II) complex [Ni(L)2](2) with SARS-CoV-2 RNA binding protein (PDB ID: 6WKP), the Omicron RBD protein (PDB ID: 7WRL) and HIV-1 protease (PDB ID: 8CI7) viruses. They bind to the active positions of viral proteins and show good inhibition performance with target viral proteins. A stronger binding was predicted between the complexes and the SARS-CoV-2 RNA, Omicron and HIV-1 viruses through the negative values of binding affinity. The binding free energies computed using a molecular docking approach were analyzed in detail and the importance of specific interactions was outlined. Furthermore, molecular docking calculations of the complexes against DNA binding protein (PDB ID: 7UV6) were also evaluated. The calculated docking results suggested that they could be adopted as potential inhibitors for the development of new anti-SARS-CoV-2 Omicron and anti-HIV drugs. [ABSTRACT FROM AUTHOR]