Repurposing benzimidazole and benzothiazole derivatives as potential inhibitors of SARS-CoV-2 : DFT, QSAR, molecular docking, molecular dynamics simulation, and in-silico pharmacokinetic and toxicity studies

Density Functional Theory (DFT) and Quantitative Structure-Activity Relationship (QSAR) studies were performed on four benzimidazoles (compounds 1–4) and two benzothiazoles (compounds 5 and 6), previously synthesized by our group. The compounds were also investigated for their binding affinity and interactions with the SARS-CoV-2 Mpro (PDB ID: 6LU7) and the human angiotensin-converting enzyme 2 (ACE2) receptor (PDB ID: 6 M18) using a molecular docking approach. Compounds 1, 2, and 3 were found to bind with equal affinity to both targets. Compound 1 showed the highest predictive docking scores, and was further subjected to molecular dynamics (MD) simulation to explain protein stability, ligand properties, and protein–ligand interactions. All compounds were assessed for their structural, physico-chemical, pharmacokinetic, and toxicological properties. Our results suggest that the investigated compounds are potential new drug leads to target SARS-CoV-2

Computational studies on potential new anti-Covid-19 agents with a multi-target mode of action

A compound that could inhibit multiple targets associated with SARS-CoV-2 infection would prove to be a drug of choice against the virus. Human receptor-ACE2, receptor binding domain (RBD) of SARS-CoV-2 S-protein, Papain-like protein of SARS-CoV-2 (PLpro), reverse transcriptase of SARS-CoV-2 (RdRp) were chosen for in silico study. A set of previously synthesized compounds (1–5) were docked into the active sites of the targets. Based on the docking score, ligand efficiency, binding free energy, and dissociation constants for a definite conformational position of the ligand, inhibitory potentials of the compounds were measured. The stability of the protein–ligand (P-L) complex was validated in silico by using molecular dynamics simulations using the YASARA suit. Moreover, the pharmacokinetic properties, FMO and NBO analysis were performed for ranking the potentiality of the compounds as drug. The geometry optimizations and electronic structures were investigated using DFT. As per the study, compound-5 has the best binding affinity against all four targets. Moreover, compounds 1, 3 and 5 are less toxic and can be considered for oral consumption

Complexes of Co(II), Ni(II), Cu(II), Fe(II), Mn(II), Cd(II) & Hg(II) with Tridentate ONN Donor Schiff Bases

434-436Complexes of the types [MLCl2H2O], [M'LCl] [M = Co(II), Ni(II), Cu(II), Mn(II), Fe(II); M' = Cd(II), Hg(II), [M”L’Cl22H2O] and [M”L’CI] [M" = Co(II), Ni(Il), Cu(II), Fe(II), Mn(II); M'" = Cd(II), Hg(II); LH = schiff base of benzoin with 2-amino-5- phenyl-l , 3, 4-oxadiazole; L'H = schiff base of benzoin with 2-amino-5-(p-anisil)-1, 3, 4-oxadiazolel have been prepared. The Co(II), Ni(II), Cu(II), Fe(II) and Mn(II) complexes are octahedral while Cd(II) and Hg(II) complexes are tetrahedral. Both the Schiff bases behave as tridentate ONN donors. The characterisation of the complexes has been done on the basis of analytical, conductance, magnetic susceptibility, molecular weight and IR, electronic, 1H NMR and ESR spectral data