In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein
Abstract Lassa fever hemorrhagic virus (LFHV) outbreaks in Nigeria continue to increase. With the possibility of a potentially deadly pandemic and the absence of a vaccine, an effective candidate drug that presents with no adverse effects and better clinical outcomes is urgently needed; hence, the a...
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Nature Portfolio
2025-08-01
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| author | Ekpo Eyo Antai Uwem Okon Edet Elizabeth N. Mbim Ini Ubi Bassey Sozan M. Abdelkhalig Francisca O. Nwaokorie Ehssan Moglad Jamda Ponmak Samia Al-Shouli Sawsan AlShouli Destiny E. Charlie Mohnad Abdalla |
| author_facet | Ekpo Eyo Antai Uwem Okon Edet Elizabeth N. Mbim Ini Ubi Bassey Sozan M. Abdelkhalig Francisca O. Nwaokorie Ehssan Moglad Jamda Ponmak Samia Al-Shouli Sawsan AlShouli Destiny E. Charlie Mohnad Abdalla |
| author_sort | Ekpo Eyo Antai |
| collection | DOAJ |
| description | Abstract Lassa fever hemorrhagic virus (LFHV) outbreaks in Nigeria continue to increase. With the possibility of a potentially deadly pandemic and the absence of a vaccine, an effective candidate drug that presents with no adverse effects and better clinical outcomes is urgently needed; hence, the aim of the study. Retrieved ligands: 5-(Methylene) evodiamine, N-(2-Fluorobenzoyl) evodiamine, N-[[2-(3-chlorophenyl)-5-(trifluoromethyl) pyrazol-3-yl]methyl]-2-(1-methyl-2,3-dihydroindol-5-yl) propanamide (NCTPMMDP), lauric acid, and sofosbuvir, and the target protein, 3MX5, were prepared and utilised for docking, molecular dynamics simulation, ADMET profiling, and DFT using standard protocols. The docking score for lauric acid was the lowest, with a value of − 6.1, followed by the standard drug and co-crystal control drug with scores of − 9.1 and − 8.9 kcal/mol, respectively. On the other hand, the scores of the other ligands ranged from − 9.5 to − 12.3 kcal/mol. Molecular simulations revealed fluctuations in the RMSD and RMSF values; however, overall, the formed complexes were stable during most of the docking simulation runs. Principal component analysis (PCA) analysis showed that all the ligands, apart from lauric acid, showed better conformational changes within the backbone of the protein. ADMET profiling showed that the ligands were better oral drug candidates than sofosbuvir, as revealed by their better absorption values and absolute compliance with the Lipinski rule of five. The DFT result showed that, apart from lauric acid, all the test ligands possess small energy gaps indicative of high reactivity. Put together, these findings indicate that the test ligands possess anti-LHFV potential that merits further in vivo and in vitro evaluations. |
| format | Article |
| id | doaj-art-766eb4d1e6ee42a49ac9fb621fc1be4a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-766eb4d1e6ee42a49ac9fb621fc1be4a2025-08-24T11:24:24ZengNature PortfolioScientific Reports2045-23222025-08-0115111710.1038/s41598-025-89989-9In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoproteinEkpo Eyo Antai0Uwem Okon Edet1Elizabeth N. Mbim2Ini Ubi Bassey3Sozan M. Abdelkhalig4Francisca O. Nwaokorie5Ehssan Moglad6Jamda Ponmak7Samia Al-Shouli8Sawsan AlShouli9Destiny E. Charlie10Mohnad Abdalla11Department of Biological (Microbiology) Oceanography, Faculty of Oceanography, University of CalabarDepartment of Biological Science (Microbiology Unit), Faculty of Natural and Applied Sciences, Arthur Jarvis UniversityDepartment of Microbiology, Faculty of Sciences, Cross River State University of Sciences and TechnologyDepartment of Microbiology, Faculty of Biological Sciences, University of CalabarDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa UniversityDepartment of Medical Laboratory Science, College of Medicine, University of LagosDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz UniversityDepartment of Molecular Biology, Federal College Veterinary and Medical Laboratory TechnologyImmunology Unit, Department of Pathology, College of Medicine, King Saud UniversityPharmacy Department, Security forces HospitalDepartment of Pure and Applied Chemistry, Faculty of Physical Sciences, University of CalabarPediatric Research Institute, Children’s Hospital Affiliated to Shandong UniversityAbstract Lassa fever hemorrhagic virus (LFHV) outbreaks in Nigeria continue to increase. With the possibility of a potentially deadly pandemic and the absence of a vaccine, an effective candidate drug that presents with no adverse effects and better clinical outcomes is urgently needed; hence, the aim of the study. Retrieved ligands: 5-(Methylene) evodiamine, N-(2-Fluorobenzoyl) evodiamine, N-[[2-(3-chlorophenyl)-5-(trifluoromethyl) pyrazol-3-yl]methyl]-2-(1-methyl-2,3-dihydroindol-5-yl) propanamide (NCTPMMDP), lauric acid, and sofosbuvir, and the target protein, 3MX5, were prepared and utilised for docking, molecular dynamics simulation, ADMET profiling, and DFT using standard protocols. The docking score for lauric acid was the lowest, with a value of − 6.1, followed by the standard drug and co-crystal control drug with scores of − 9.1 and − 8.9 kcal/mol, respectively. On the other hand, the scores of the other ligands ranged from − 9.5 to − 12.3 kcal/mol. Molecular simulations revealed fluctuations in the RMSD and RMSF values; however, overall, the formed complexes were stable during most of the docking simulation runs. Principal component analysis (PCA) analysis showed that all the ligands, apart from lauric acid, showed better conformational changes within the backbone of the protein. ADMET profiling showed that the ligands were better oral drug candidates than sofosbuvir, as revealed by their better absorption values and absolute compliance with the Lipinski rule of five. The DFT result showed that, apart from lauric acid, all the test ligands possess small energy gaps indicative of high reactivity. Put together, these findings indicate that the test ligands possess anti-LHFV potential that merits further in vivo and in vitro evaluations.https://doi.org/10.1038/s41598-025-89989-9Lassa fever virusDFTDockingSimulationNucleoproteinNigeria |
| spellingShingle | Ekpo Eyo Antai Uwem Okon Edet Elizabeth N. Mbim Ini Ubi Bassey Sozan M. Abdelkhalig Francisca O. Nwaokorie Ehssan Moglad Jamda Ponmak Samia Al-Shouli Sawsan AlShouli Destiny E. Charlie Mohnad Abdalla In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein Scientific Reports Lassa fever virus DFT Docking Simulation Nucleoprotein Nigeria |
| title | In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein |
| title_full | In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein |
| title_fullStr | In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein |
| title_full_unstemmed | In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein |
| title_short | In-silico screening of small compounds against Lassa fever haemorrhagic virus nucleoprotein |
| title_sort | in silico screening of small compounds against lassa fever haemorrhagic virus nucleoprotein |
| topic | Lassa fever virus DFT Docking Simulation Nucleoprotein Nigeria |
| url | https://doi.org/10.1038/s41598-025-89989-9 |
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