دورية أكاديمية
أعرض في EDS

Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses.

التفاصيل البيبلوغرافية
العنوان: Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses.
المؤلفون: Suleman M; Laboratory of Animal Research Center (LARC), Qatar University, Doha, Qatar; Center for Biotechnology and Microbiology, University of Swat, Swat, Pakistan. Electronic address: suleman@uswat.edu.pk., Sayaf AM; School of Chemical Sciences, Universiti Sains Malaysia, Gelugor, Penang, Malaysia. Electronic address: amsayaf@gmail.com., Khan A; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: abbas.khan@qu.edu.qa., Khan SA; Tunneling Group, Biotechnology Centre, Doctoral School, Silesian University of Technology, Akademicka 2, 44-100 Gliwice, Poland. Electronic address: salman.ali@polsl.pl., Albekairi NA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: nalbekairi@ksu.edu.sa., Alshammari A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: abdshammari@ksu.edu.sa., Agouni A; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: aagouni@qu.edu.qa., Yassine HM; Biomedical Research Center, Qatar University, 2713 Doha, Qatar; College of Health Sciences-QU Health, Qatar University, 2713 Doha, Qatar. Electronic address: hyassine@qu.edu.qa., Crovella S; Laboratory of Animal Research Center (LARC), Qatar University, Doha, Qatar. Electronic address: sgrovella@qu.edu.qa.
المصدر: Journal of infection and public health [J Infect Public Health] 2024 Jul; Vol. 17 (7), pp. 102448. Date of Electronic Publication: 2024 May 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 101487384 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1876-035X (Electronic) Linking ISSN: 18760341 NLM ISO Abbreviation: J Infect Public Health Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Elsevier, 2008-
مواضيع طبية MeSH: Tripartite Motif Proteins*/metabolism , Tripartite Motif Proteins*/genetics , Tripartite Motif Proteins*/chemistry , Viral Nonstructural Proteins*/chemistry , Viral Nonstructural Proteins*/metabolism , Viral Nonstructural Proteins*/genetics , Molecular Docking Simulation* , Ubiquitin-Protein Ligases*/metabolism , Protein Binding*, Humans ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Transcription Factors/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; Influenza A virus/drug effects ; Influenza A virus/immunology ; Phytochemicals/pharmacology ; Phytochemicals/chemistry ; Drug Design ; Drug Evaluation, Preclinical
مستخلص: Background: Influenza 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.
Methods: In 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.
Results: The 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.
Conclusion: Our 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
فهرسة مساهمة: Keywords: Host immunity; Influenza A NS1; Molecular dynamics; Natural Products Databases; TRIM25
المشرفين على المادة: 0 (Tripartite Motif Proteins)
0 (Viral Nonstructural Proteins)
EC 2.3.2.27 (TRIM25 protein, human)
0 (INS1 protein, influenza virus)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
0 (Transcription Factors)
0 (Antiviral Agents)
0 (Phytochemicals)
تواريخ الأحداث: Date Created: 20240530 Date Completed: 20240620 Latest Revision: 20240702
رمز التحديث: 20240703
DOI: 10.1016/j.jiph.2024.05.005
PMID: 38815532
قاعدة البيانات: MEDLINE
الوصف
تدمد:1876-035X
DOI:10.1016/j.jiph.2024.05.005