Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations
Introduction: Ebola virus (EBOV) is a highly lethal RNA virus that causes severe hemorrhagic fever in humans and non-human primates. The lack of effective treatment or vaccine for this pathogen poses a serious threat to a global pandemic. Therefore, it is imperative to explore new drugs and therapie...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Journal of Infection and Public Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1876034124003708 |
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| author | Abbas Khan Abrar Mohammad Sayaf Anwar Mohammad Fahad M. Alshabrmi Tarek Benameur Dong-Qing Wei Kar Kheng Yeoh Abdelali Agouni |
| author_facet | Abbas Khan Abrar Mohammad Sayaf Anwar Mohammad Fahad M. Alshabrmi Tarek Benameur Dong-Qing Wei Kar Kheng Yeoh Abdelali Agouni |
| author_sort | Abbas Khan |
| collection | DOAJ |
| description | Introduction: Ebola virus (EBOV) is a highly lethal RNA virus that causes severe hemorrhagic fever in humans and non-human primates. The lack of effective treatment or vaccine for this pathogen poses a serious threat to a global pandemic. Therefore, it is imperative to explore new drugs and therapies to combat this life-threatening infection. Materials and methods: In this study, we employed in silico methods to assess the inhibitory activity of natural products from traditional Chinese medicine (TCM) against four EBOV proteins that are crucial for viral replication and assembly: VP40, VP35, VP30, and VP24. We performed molecular docking of TCM compounds with the EBOV proteins and screened them based on their docking scores, binding free energies, and pharmacokinetic properties. Results: Our results pinpointed eight TCM compounds (TCM1797, TCM2872, TCM250, TCM2837, TCM2644, TCM4697, TCM2322, and TCM277) that exhibited superior efficacy in inhibiting all the EBOV proteins compared to the controls. These compounds interacted with key residues of the EBOV proteins through various types of bonds, such as hydrogen bonds, salt bridges, and π-π interactions, forming stable complexes that could disrupt the function of the EBOV proteins. These compounds were found to possess known antiviral activity, acceptable pharmacokinetic properties, and human usage history, which make them promising candidates for anti-EBOV drug development. Moreover, the molecular simulation analysis confirmed the binding stability, structural compactness, and residue flexibility properties of these compounds. Furthermore, the binding free energy results revealed that VP30-TCM2644, VP30-TCM4697, VP35-TCM2837, VP24-TCM250, and VP24-TCM277 complexes exhibit significant binding free energy values compared to the control ligands. Principal Component Analysis (PCA) and Free Energy Landscape (FEL) results revealed the trajectories' motion and conformational energy states. Conclusions: Our findings provide valuable insights into the molecular mechanisms driving the efficacy of TCM drugs against EBOV and suggest novel approaches for the development of anti-EBOV therapies. |
| format | Article |
| id | doaj-art-1108899c95744cd095e02c268b52754a |
| institution | Kabale University |
| issn | 1876-0341 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Infection and Public Health |
| spelling | doaj-art-1108899c95744cd095e02c268b52754a2025-01-21T04:12:58ZengElsevierJournal of Infection and Public Health1876-03412025-02-01182102636Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculationsAbbas Khan0Abrar Mohammad Sayaf1Anwar Mohammad2Fahad M. Alshabrmi3Tarek Benameur4Dong-Qing Wei5Kar Kheng Yeoh6Abdelali Agouni7Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Division of Bioinformatics, Department of Biomedical Sciences, School of Medical and Life Sciences, Sunway University, 5, Jalan Universiti, Bandar Sunway, 47500 Petaling Jaya, Selangor, MalaysiaSchool of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, MalaysiaDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman, KuwaitDepartment of Medical laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi ArabiaDepartment of Biomedical Sciences, College of Medicine, King Faisal University, Al Ahsa 31982, Saudi ArabiaState Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia; Corresponding author.Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Correspondence to: Department of Pharmaceutical Sciences, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.Introduction: Ebola virus (EBOV) is a highly lethal RNA virus that causes severe hemorrhagic fever in humans and non-human primates. The lack of effective treatment or vaccine for this pathogen poses a serious threat to a global pandemic. Therefore, it is imperative to explore new drugs and therapies to combat this life-threatening infection. Materials and methods: In this study, we employed in silico methods to assess the inhibitory activity of natural products from traditional Chinese medicine (TCM) against four EBOV proteins that are crucial for viral replication and assembly: VP40, VP35, VP30, and VP24. We performed molecular docking of TCM compounds with the EBOV proteins and screened them based on their docking scores, binding free energies, and pharmacokinetic properties. Results: Our results pinpointed eight TCM compounds (TCM1797, TCM2872, TCM250, TCM2837, TCM2644, TCM4697, TCM2322, and TCM277) that exhibited superior efficacy in inhibiting all the EBOV proteins compared to the controls. These compounds interacted with key residues of the EBOV proteins through various types of bonds, such as hydrogen bonds, salt bridges, and π-π interactions, forming stable complexes that could disrupt the function of the EBOV proteins. These compounds were found to possess known antiviral activity, acceptable pharmacokinetic properties, and human usage history, which make them promising candidates for anti-EBOV drug development. Moreover, the molecular simulation analysis confirmed the binding stability, structural compactness, and residue flexibility properties of these compounds. Furthermore, the binding free energy results revealed that VP30-TCM2644, VP30-TCM4697, VP35-TCM2837, VP24-TCM250, and VP24-TCM277 complexes exhibit significant binding free energy values compared to the control ligands. Principal Component Analysis (PCA) and Free Energy Landscape (FEL) results revealed the trajectories' motion and conformational energy states. Conclusions: Our findings provide valuable insights into the molecular mechanisms driving the efficacy of TCM drugs against EBOV and suggest novel approaches for the development of anti-EBOV therapies.http://www.sciencedirect.com/science/article/pii/S1876034124003708Ebola virusDocking virtual screeningNatural productsMolecular simulationPharmacokinetic studies |
| spellingShingle | Abbas Khan Abrar Mohammad Sayaf Anwar Mohammad Fahad M. Alshabrmi Tarek Benameur Dong-Qing Wei Kar Kheng Yeoh Abdelali Agouni Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations Journal of Infection and Public Health Ebola virus Docking virtual screening Natural products Molecular simulation Pharmacokinetic studies |
| title | Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations |
| title_full | Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations |
| title_fullStr | Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations |
| title_full_unstemmed | Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations |
| title_short | Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations |
| title_sort | discovery of anti ebola virus multi target inhibitors from traditional chinese medicine database using molecular screening biophysical investigation and binding free energy calculations |
| topic | Ebola virus Docking virtual screening Natural products Molecular simulation Pharmacokinetic studies |
| url | http://www.sciencedirect.com/science/article/pii/S1876034124003708 |
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