Molecular docking-assisted investigation of Pd(II) complexes carrying "SNS" pincer-type pyridine-thioether ligand as potential drug candidates against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has posed a threat to public health throughout the world since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was discovered in late 2019. Since the beginning of the pandemic, scientists have done a tremendous amount of work in this area. However, among these studies, the investigation of the effect of newly synthesized compounds against coronavirus is rather weak. Examining the newly synthesized compounds with a computer-assisted molecular docking study provides quite an advantage in terms of the estimation and analysis of the biochemical activity and binding affinity of existing synthesized compounds against a biological target in a labor, time, and cost-saving way. In this study, the SNS pincer type 2,6-bis[[(4-methylphenyl)thio]methyl]pyridine ligand(L) (1) and its novel Pd(II) complexes ([Pd(κ-L)(OAc)]·3HO (2) and [Pd(κ-L)Cl]·3HO (3)) were synthesized and characterized by using FT-IR, UV-Vis, NMR, mass and elemental analysis techniques. The synthesized Pd complexes exhibited a square planar structure. The compounds were found to have non-electrolytic behavior. In the meantime, in silico investigations have defined and justified interaction processes between these molecules and Pd(II) at the atomic level. Furthermore, using molecular docking against target proteins of SARS-CoV-2, the efficiency of the SNS pincer type ligand and its Pd (II) complexes produced was studied and discussed for the first time. The experimental data has been supported and illuminated using computational visual methods and molecular docking, and the findings produced indicate compatibility. The binding energy values of the relevant compounds on the four protein model structures of SARS-CoV-2 (Main Protease, Papain-like protease, RdRp without RNA, and RdRp with RNA) are represented. Compound 2 ([Pd(κ-L)(OAc)]·3HO) is the structure that exhibits the highest biochemical activity. According to all of the docking studies, Papain-like protease is the SARS-CoV-2 protein with which the three compounds exhibit mutual interaction. The compound 2 structure, in particular, is the most effective in terms of structural and interaction with the targets, as well as binding orientations.