Phytochemical and Antiviral Investigation of Centaurothamnus maximus : Discovery of Repdiolidetriol as a Dual Anti‐HAV and Anti‐HSV‐1 Candidate

ABSTRACT Repdiolidetriol ( 1 ), hydroxyjanerin ( 2 ), and 5‐ O ‐caffeoylquinic acid methyl ester ( 3 ) were isolated and characterized from the aerial parts of Centaurothamnus maximus Wagenitz & Dittrich (Asteraceae), a rare and underexplored genus. The antiviral potential of the compounds was assessed against hepatitis A virus (HAV) and herpes simplex virus type 1 (HSV‐1) using a cytopathic effect inhibition assay. Among the isolates, repdiolidetriol ( 1 ), a guaianolide sesquiterpene lactone, exhibited remarkable antiviral activity against HAV (EC 50 = 5.87 ± 0.19 µM, selectivity index [SI] = 12.5) and HSV‐1 (EC 50 = 6.89 ± 0.43 µM, SI = 10.6). Mechanistic studies revealed that repdiolidetriol inhibited HSV‐1 predominantly through the suppression of viral replication, with additional effects on adsorption and lesser virucidal potency. Molecular docking studies further confirmed its interaction with HSV‐1 glycoprotein B and DNA polymerase receptors, highlighting its proposed dual‐site interaction and potential multitarget antiviral potential. This is the first time for isolation of repdiolidetriol and 5‐ O ‐caffeoylquinic acid methyl ester from this genus and the first report to demonstrate the antiviral properties of repdiolidetriol, expanding its phytochemical profile and offering new promising candidates for future antiviral drug development.