Identification of a Novel N-terminal Domain Nucleocapsid of SARS-CoV-2 Inhibitors Using in Silico Virtual Screening. | ||||
| Bulletin of Pharmaceutical Sciences Assiut University | ||||
| Articles in Press, Accepted Manuscript, Available Online from 28 April 2025 | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/bfsa.2025.352750.2404 | ||||
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| Authors | ||||
Derouicha MATMOUR  1; Mimouna BEKKADOUR1; Dalila MIRAOUI 2; Nezha SEKKAL3; Saliha BENABDI4; Ahmed Oughilas1; Chahrazed KANDOUCI5; Yassine MERAD6
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| 1Department of Pharmacy, University of Sidi Bel-Abbes, 22000, Algeria | ||||
| 2Oncology Department, Anticancer Center of Sidi Bel-Abbès, 22000, Algeria | ||||
| 3- Département de Pharmacie, Faculté de Médecine Taleb Mourad - Civil Engineering and Environmental Laboratory, CEEL - Université Djillali Liabes, Sidi Bel Abbes, Algérie | ||||
| 4Pediatric Intensive Care Department, EHS Canastel, Faculty of Medicine, University of Oran 1, 31000, Algeria | ||||
| 5Environment and health research laboratory, Djillali Liabès University of Sidi Bel Abbès, 22000, Algeria | ||||
| 6Central Laboratory, University Hospital Center of Sidi Bel-Abbes, 22000, Algeria. | ||||
| Abstract | ||||
| SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. Protein-targeted therapeutics are currently unavailable for this virus. In this research, we apply a molecular docking approach to identify inhibitors of the N protein that can be used as antiviral medications. This work summarizes the virtual screening of 46 compounds, divided into 27 drugs and 19 bioactive chemicals coumponds to find prospective therapeutic inhibitors targeting the 2.7 Å crystal structure of the SARS-CoV-2 N protein N-terminal domain (PDB ID: 6M3M). Multiple computational techniques were used in this study to investigate the probable mechanisms of binding and inhibitor activity of the top five medicines and top five bioactive chemicals compounds against NTD-N protein. Suramin had the highest binding affinity (-11.1 kcal/mol) among the top five anti-N drugs, and Strictinin and 4,5-Dicaffeoylquinic acid had the highest binding affinity (-9 kcal/mol) among the top five anti-N bioactive chemicals compounds. Following that, the druglikness study of the selected Lipinski rule of the top five inhibitors revealed that the 4E1Rcat and Crambescidin 359 did not violate any other Lipinski characteristics and have bioaviabilities of 0.56 and 0.55, respectively. Also, the prediction of gastrointestinal absorption and brain access showed that only the 4A1Rcat and Crambescidin 359 have a good result. These tow coumponds can be an effectives drugs against the target NTD-N protein. Finally, the residues A:Thr 92, B:Lys 66, B:Trp 133, and A:Arg 89, A:Tyr 112 influenced RNA dynamics and binding, with B:Lys 66, A:Arg 89 having the strongest interactions. | ||||
| Keywords | ||||
| SARS-CoV-2; Nucleocapsid protein; N-terminal domain; Molecular docking; Druglikness | ||||
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