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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.

ABSTRACT: 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 M^pro (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.

SUBMITTER: Mohapatra RK

PROVIDER: S-EPMC8496942 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Mohapatra Ranjan K RK Dhama Kuldeep K El-Arabey Amr Ahmed AA Sarangi Ashish K AK Tiwari Ruchi R Emran Talha Bin TB Azam Mohammad M Al-Resayes Saud I SI Raval Mukesh K MK Seidel Veronique V Abdalla Mohnad M

Journal of King Saud University. Science 20211007 8

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 M<sup>pro</sup> (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 w ...[more]

PMID: 34642560

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Dataset Information

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.

Publications

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

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