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 i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364721002998 |
| _version_ | 1818932477198073856 |
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| author | Ranjan K. Mohapatra Kuldeep Dhama Amr Ahmed El–Arabey Ashish K. Sarangi Ruchi Tiwari Talha Bin Emran Mohammad Azam Saud I. Al-Resayes Mukesh K. Raval Veronique Seidel Mohnad Abdalla |
| author_facet | Ranjan K. Mohapatra Kuldeep Dhama Amr Ahmed El–Arabey Ashish K. Sarangi Ruchi Tiwari Talha Bin Emran Mohammad Azam Saud I. Al-Resayes Mukesh K. Raval Veronique Seidel Mohnad Abdalla |
| author_sort | Ranjan K. Mohapatra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T04:33:06Z |
| format | Article |
| id | doaj.art-19f3914ae3da4a4d98dc0f4a3dd14e0c |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-12-20T04:33:06Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-19f3914ae3da4a4d98dc0f4a3dd14e0c2022-12-21T19:53:19ZengElsevierJournal of King Saud University: Science1018-36472021-12-01338101637Repurposing benzimidazole and benzothiazole derivatives as potential inhibitors of SARS-CoV-2: DFT, QSAR, molecular docking, molecular dynamics simulation, and in-silico pharmacokinetic and toxicity studiesRanjan K. Mohapatra0Kuldeep Dhama1Amr Ahmed El–Arabey2Ashish K. Sarangi3Ruchi Tiwari4Talha Bin Emran5Mohammad Azam6Saud I. Al-Resayes7Mukesh K. Raval8Veronique Seidel9Mohnad Abdalla10Department of Chemistry, Government College of Engineering, Keonjhar, Odisha 758002, IndiaDivision of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, IndiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, EgyptDepartment of Chemistry, School of Applied Sciences, Centurion University of Technology and Management, Odisha, IndiaDepartment of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura 281001, IndiaDepartment of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, BangladeshDepartment of Chemistry, College of Science, King Saud University, PO BOX 2455, Riyadh 11451, Saudi Arabia; Corresponding authors.Department of Chemistry, College of Science, King Saud University, PO BOX 2455, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, G. M. University, Sambalpur, Odisha, IndiaNatural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom; Corresponding authors.Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, PR China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1018364721002998DFTQSARSARS-CoV-2 MproACE2Molecular dockingMD simulation |
| spellingShingle | Ranjan K. Mohapatra Kuldeep Dhama Amr Ahmed El–Arabey Ashish K. Sarangi Ruchi Tiwari Talha Bin Emran Mohammad Azam Saud I. Al-Resayes Mukesh K. Raval Veronique Seidel Mohnad Abdalla 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 Journal of King Saud University: Science DFT QSAR SARS-CoV-2 Mpro ACE2 Molecular docking MD simulation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | DFT QSAR SARS-CoV-2 Mpro ACE2 Molecular docking MD simulation |
| url | http://www.sciencedirect.com/science/article/pii/S1018364721002998 |
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