Discovery of acyclic purine nucleosides as promising antiviral agents against dengue virus.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Discovery of acyclic purine nucleosides as promising antiviral agents against dengue virus.
Συγγραφείς: Mondal SK; Indian Institute of Technology Bhubaneswar, Department of Chemistry, Jatni, Khordha, Odisha 752050, India., Samantaray S; Institute of Life Sciences (ILS), Department of Biotechnology, NALCO Nagar, Bhubaneswar, Odisha 751023, India., Sahoo AS; Institute of Life Sciences (ILS), Department of Biotechnology, NALCO Nagar, Bhubaneswar, Odisha 751023, India., Mohapatra A; Thapar Institute of Engineering and Technology (TIET), School of Chemistry and Biochemistry, Patiala 147004, Punjab, India., Syed GH; Institute of Life Sciences (ILS), Department of Biotechnology, NALCO Nagar, Bhubaneswar, Odisha 751023, India. Electronic address: gulamsyed@ils.res.in., Pal S; Indian Institute of Technology Bhubaneswar, Department of Chemistry, Jatni, Khordha, Odisha 752050, India. Electronic address: spal@iitbbs.ac.in.
Πηγή: Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109961. Date of Electronic Publication: 2026 May 09.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: New York, London, Academic Press.
Ιατρικοί όροι (MeSH): Antiviral Agents*/pharmacology , Antiviral Agents*/chemistry , Antiviral Agents*/chemical synthesis , Dengue Virus*/drug effects , Purine Nucleosides*/pharmacology , Purine Nucleosides*/chemistry , Purine Nucleosides*/chemical synthesis , Drug Discovery*, Humans ; Structure-Activity Relationship ; Molecular Docking Simulation ; Molecular Structure ; Microbial Sensitivity Tests ; Dose-Response Relationship, Drug
Περίληψη: Dengue virus (DENV) remains a significant global health challenge as one of the most prevalent mosquito-borne viral infections, with no specific antiviral therapy currently approved. Acyclic purine nucleosides have demonstrated as broad-spectrum antiviral activity by interfering with viral genome replication. Therefore, in this study, we designed a new series of d-glucose-derived acyclic purine nucleoside analogues (5a-f, 6a-c, and 8a-b), and evaluated their inhibitory activity against DENV serotype 2 (DENV2) using an in vitro Huh-7 cell-based assay. Among the library, analogue 5e exhibited the strongest antiviral profile, displaying a CC50 of 153 μM and an EC50 of 13.64 μM, resulting a favorable selectivity index. Molecular docking and 100-ns MD simulations supported a stable NS5 GTP/capping-site binding mode for 5e, and ADMET-guided SAR analysis highlighted lipophilicity, permeability, and hydrogen-bond acceptors as key determinants of antiviral potency and developability across the series. These results highlight the potential of acyclic purine nucleosides as a promising scaffold for the development of anti-dengue therapeutics.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
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.
Contributed Indexing: Keywords: ADMET prediction; Acyclic purine nucleosides; Dengue virus; Docking studies; Molecular dynamics simulation
Substance Nomenclature: 0 (Antiviral Agents)
0 (Purine Nucleosides)
Entry Date(s): Date Created: 20260513 Date Completed: 20260716 Latest Revision: 20260716
Update Code: 20260717
DOI: 10.1016/j.bioorg.2026.109961
PMID: 42127740
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1090-2120
DOI:10.1016/j.bioorg.2026.109961