Conformational dynamics and binding free energy analyses unveil a stable flavonoid inhibitor of dengue virus NS5 polymerase.

ABSTRACT: The persistent global spread of dengue virus (DENV) necessitates the identification of novel antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) domain of the non-structural protein 5 (NS5) is a validated target for therapy due to its critical roles in viral genome replication. In this study, we used a structure-guided virtual screening approach to identify potent phytochemical inhibitors of DENV RdRp from the Plant Secondary Compound Database (PSC-db) by focusing on 326 flavonoids. Following drug-likeness filtering and hierarchical docking with MM-GBSA analysis, five top candidates were identified, with PSCdb01560 emerging as the most promising. Subsequent molecular dynamics simulations over 500 ns revealed PSCdb01560's exceptional binding stability, characterised by low prote

SUBMITTER: Alsaady IM 

PROVIDER: S-EPMC12949254 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature