Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa
BackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin condition of the terminal hair follicle, which can present in sporadic, familial, or syndromic forms. The exact pathogenesis of HS remains elusive, posing a challenge for the development of effective treatments. Among the various...
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| التنسيق: | article |
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2025
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| الوصول للمادة أونلاين: | http://dx.doi.org/10.1016/j.jiph.2025.102697 https://www.sciencedirect.com/science/article/pii/S1876034125000462 http://hdl.handle.net/10576/64069 |
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| _version_ | 1857415085050298368 |
|---|---|
| author | Muhammad, Suleman |
| author2 | Murshed, Abduh Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Tricarico, Paola Maura Moltrasio, Chiara Agouni, Abdelali Yeoh, Kar Kheng Marzano, Angelo Valerio Crovella, Sergio |
| author2_role | author author author author author author author author author author |
| author_facet | Muhammad, Suleman Murshed, Abduh Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Tricarico, Paola Maura Moltrasio, Chiara Agouni, Abdelali Yeoh, Kar Kheng Marzano, Angelo Valerio Crovella, Sergio |
| author_role | author |
| dc.creator.none.fl_str_mv | Muhammad, Suleman Murshed, Abduh Sayaf, Abrar Mohammad Khan, Abbas Khan, Salman Ali Tricarico, Paola Maura Moltrasio, Chiara Agouni, Abdelali Yeoh, Kar Kheng Marzano, Angelo Valerio Crovella, Sergio |
| dc.date.none.fl_str_mv | 2025-04-08T09:34:57Z 2025-04 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.jiph.2025.102697 Suleman, M., Murshed, A., Sayaf, A. M., Khan, A., Khan, S. A., Tricarico, P. M., ... & Crovella, S. (2025). Exploring Global Natural Product Databases for NLRP3 Inhibition: Unveiling novel combinatorial therapeutic strategy for Hidradenitis Suppurativa. Journal of Infection and Public Health, 102697. 1876-0341 https://www.sciencedirect.com/science/article/pii/S1876034125000462 http://hdl.handle.net/10576/64069 4 18 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/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Hidradenitis suppurativa NLRP3 Drug screening Molecular dynamics simulation |
| dc.title.none.fl_str_mv | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | BackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin condition of the terminal hair follicle, which can present in sporadic, familial, or syndromic forms. The exact pathogenesis of HS remains elusive, posing a challenge for the development of effective treatments. Among the various immunological mechanisms, the NLRP3 inflammasome is thought to contribute to the pathogenesis of HS, releasing cytokines such as IL-1β and IL-18 which initiates and exacerbates inflammation. Consequently, targeting NLRP3 offers a potential strategy for mitigating inflammation in HS-affected skin. MethodsIn this study we used the docking, molecular dynamics simulation and binding free energy approaches to identify the potent inhibitor of NLRP3 by screening the African phytocompounds and traditional Chinese medicine databases. ResultsOur virtual drug screening analysis identified two lead compounds from each database, characterized by high docking scores such as SA-21676268 (-8.135 kcal/mol), SA-167673 (-10.251 kcal/mol), EA-45360194 (-10.376 kcal/mol), EA-46881231 (-10.011 kcal/mol), NEA-44258150 (-9.856 kcal/mol), NEA-135926572 (-7.662 kcal/mol), NA-163089376 (-9.237 kcal/mol), NA-440735 (-8.826 kcal/mol), TCM-392442 (-10.438 kcal/mol), and TCM-10043097 (-9.046 kcal/mol) which highlighted the strong binding affinity as compared to the control NP3–146 drug (-5.09 kcal/mol). Moreover, the values of dissociation constant further validated the strong binding affinity between the identified lead compounds and NLRP3. The dynamic stability and strong bonding energies of the lead compounds-NLRP3 complexes were confirmed by the molecular dynamic simulation and binding free energy calculation. The analysis of ADMET properties for all compounds indicated high intestinal absorption, water solubility, absence of hepatotoxicity, and skin sensitivity. ConclusionIn conclusion, our molecular simulations and binding free energy calculations confirmed the strong affinity of these lead compounds for NLRP3 as compared to the control drug, highlighting their potential as part of a combinatorial therapeutic strategy for HS to effectively reduce disease-related inflammation. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_44da1c17ddde1e3c6a11428d9f396f55 |
| identifier_str_mv | Suleman, M., Murshed, A., Sayaf, A. M., Khan, A., Khan, S. A., Tricarico, P. M., ... & Crovella, S. (2025). Exploring Global Natural Product Databases for NLRP3 Inhibition: Unveiling novel combinatorial therapeutic strategy for Hidradenitis Suppurativa. Journal of Infection and Public Health, 102697. 1876-0341 4 18 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:10576/64069 |
| publishDate | 2025 |
| 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/4.0/ |
| spelling | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativaMuhammad, SulemanMurshed, AbduhSayaf, Abrar MohammadKhan, AbbasKhan, Salman AliTricarico, Paola MauraMoltrasio, ChiaraAgouni, AbdelaliYeoh, Kar KhengMarzano, Angelo ValerioCrovella, SergioHidradenitis suppurativaNLRP3Drug screeningMolecular dynamics simulationBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin condition of the terminal hair follicle, which can present in sporadic, familial, or syndromic forms. The exact pathogenesis of HS remains elusive, posing a challenge for the development of effective treatments. Among the various immunological mechanisms, the NLRP3 inflammasome is thought to contribute to the pathogenesis of HS, releasing cytokines such as IL-1β and IL-18 which initiates and exacerbates inflammation. Consequently, targeting NLRP3 offers a potential strategy for mitigating inflammation in HS-affected skin. MethodsIn this study we used the docking, molecular dynamics simulation and binding free energy approaches to identify the potent inhibitor of NLRP3 by screening the African phytocompounds and traditional Chinese medicine databases. ResultsOur virtual drug screening analysis identified two lead compounds from each database, characterized by high docking scores such as SA-21676268 (-8.135 kcal/mol), SA-167673 (-10.251 kcal/mol), EA-45360194 (-10.376 kcal/mol), EA-46881231 (-10.011 kcal/mol), NEA-44258150 (-9.856 kcal/mol), NEA-135926572 (-7.662 kcal/mol), NA-163089376 (-9.237 kcal/mol), NA-440735 (-8.826 kcal/mol), TCM-392442 (-10.438 kcal/mol), and TCM-10043097 (-9.046 kcal/mol) which highlighted the strong binding affinity as compared to the control NP3–146 drug (-5.09 kcal/mol). Moreover, the values of dissociation constant further validated the strong binding affinity between the identified lead compounds and NLRP3. The dynamic stability and strong bonding energies of the lead compounds-NLRP3 complexes were confirmed by the molecular dynamic simulation and binding free energy calculation. The analysis of ADMET properties for all compounds indicated high intestinal absorption, water solubility, absence of hepatotoxicity, and skin sensitivity. ConclusionIn conclusion, our molecular simulations and binding free energy calculations confirmed the strong affinity of these lead compounds for NLRP3 as compared to the control drug, highlighting their potential as part of a combinatorial therapeutic strategy for HS to effectively reduce disease-related inflammation.This work was supported by Qatar University grant No. QUPD CAS-23-24491. This research was partially supported by Italian Ministry of Health (Ricerca Corrente) of Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan (Italy).Elsevier2025-04-08T09:34:57Z2025-04Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jiph.2025.102697Suleman, M., Murshed, A., Sayaf, A. M., Khan, A., Khan, S. A., Tricarico, P. M., ... & Crovella, S. (2025). Exploring Global Natural Product Databases for NLRP3 Inhibition: Unveiling novel combinatorial therapeutic strategy for Hidradenitis Suppurativa. Journal of Infection and Public Health, 102697.1876-0341https://www.sciencedirect.com/science/article/pii/S1876034125000462http://hdl.handle.net/10576/640694181876-035Xenhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/640692025-04-08T19:07:39Z |
| spellingShingle | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa Muhammad, Suleman Hidradenitis suppurativa NLRP3 Drug screening Molecular dynamics simulation |
| status_str | publishedVersion |
| title | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| title_full | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| title_fullStr | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| title_full_unstemmed | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| title_short | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| title_sort | Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa |
| topic | Hidradenitis suppurativa NLRP3 Drug screening Molecular dynamics simulation |
| url | http://dx.doi.org/10.1016/j.jiph.2025.102697 https://www.sciencedirect.com/science/article/pii/S1876034125000462 http://hdl.handle.net/10576/64069 |