Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa

IF 4.7 3区医学 Q1 INFECTIOUS DISEASES Journal of Infection and Public Health Pub Date : 2025-02-13 DOI:10.1016/j.jiph.2025.102697

Muhammad Suleman , Abduh Murshed , Abrar Mohammad Sayaf , Abbas Khan , Salman Ali Khan , Paola Maura Tricarico , Chiara Moltrasio , Abdelali Agouni , Kar Kheng Yeoh , Angelo Valerio Marzano , Sergio Crovella

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Abstract

Background

Hidradenitis 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.

Methods

In 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.

Results

Our 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.

Conclusion

In 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.

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来源期刊

Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES

CiteScore

13.10

自引率

1.50%

发文量

203

审稿时长

96 days

期刊介绍： The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.