Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses
BackgroundInfluenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin ch...
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2024
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| Online Access: | http://dx.doi.org/10.1016/j.jiph.2024.05.005 https://www.sciencedirect.com/science/article/pii/S187603412400145X http://hdl.handle.net/10576/59371 |
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| _version_ | 1857415087318368256 |
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| author | Muhammad, Suleman |
| author2 | Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Albekairi, Norah A. Alshammari, Abdulrahman Agouni, Abdelali Yassine, Hadi M. Crovella, Sergio |
| author2_role | author author author author author author author author |
| author_facet | Muhammad, Suleman Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Albekairi, Norah A. Alshammari, Abdulrahman Agouni, Abdelali Yassine, Hadi M. Crovella, Sergio |
| author_role | author |
| dc.creator.none.fl_str_mv | Muhammad, Suleman Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Albekairi, Norah A. Alshammari, Abdulrahman Agouni, Abdelali Yassine, Hadi M. Crovella, Sergio |
| dc.date.none.fl_str_mv | 2024-09-26T11:03:11Z 2024-07 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.jiph.2024.05.005 Suleman, M., Sayaf, A. M., Khan, A., Khan, S. A., Albekairi, N. A., Alshammari, A., ... & Crovella, S. (2024). Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses. Journal of Infection and Public Health, 17(7), 102448. 1876-0341 https://www.sciencedirect.com/science/article/pii/S187603412400145X http://hdl.handle.net/10576/59371 7 17 1876-035X |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Influenza A NS1 TRIM25 Molecular dynamics Natural Products Databases Host immunity |
| dc.title.none.fl_str_mv | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | BackgroundInfluenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. MethodsIn our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. ResultsThe molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski’s rule. ConclusionOur molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_d8d76ccec821ccf3a29cf7461579bcfd |
| identifier_str_mv | Suleman, M., Sayaf, A. M., Khan, A., Khan, S. A., Albekairi, N. A., Alshammari, A., ... & Crovella, S. (2024). Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses. Journal of Infection and Public Health, 17(7), 102448. 1876-0341 7 17 1876-035X |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/59371 |
| publishDate | 2024 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spelling | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responsesMuhammad, SulemanSayaf, Abrar MohammadKhan, AbbasKhan, Salman AliAlbekairi, Norah A.Alshammari, AbdulrahmanAgouni, AbdelaliYassine, Hadi M.Crovella, SergioInfluenza A NS1TRIM25Molecular dynamicsNatural Products DatabasesHost immunityBackgroundInfluenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. MethodsIn our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. ResultsThe molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski’s rule. ConclusionOur molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections.This work was supported by Qatar University grant No. QUPD\u2010CAS\u201023\u201024\u2010491.It was also supported by the Researchers Supporting Project number (RSPD2024R1035), King Saud University, Riyadh, Saudi Arabia.Elsevier2024-09-26T11:03:11Z2024-07Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jiph.2024.05.005Suleman, M., Sayaf, A. M., Khan, A., Khan, S. A., Albekairi, N. A., Alshammari, A., ... & Crovella, S. (2024). Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses. Journal of Infection and Public Health, 17(7), 102448.1876-0341https://www.sciencedirect.com/science/article/pii/S187603412400145Xhttp://hdl.handle.net/10576/593717171876-035Xenhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/593712024-09-26T19:07:13Z |
| spellingShingle | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses Muhammad, Suleman Influenza A NS1 TRIM25 Molecular dynamics Natural Products Databases Host immunity |
| status_str | publishedVersion |
| title | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| title_full | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| title_fullStr | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| title_full_unstemmed | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| title_short | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| title_sort | Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses |
| topic | Influenza A NS1 TRIM25 Molecular dynamics Natural Products Databases Host immunity |
| url | http://dx.doi.org/10.1016/j.jiph.2024.05.005 https://www.sciencedirect.com/science/article/pii/S187603412400145X http://hdl.handle.net/10576/59371 |