Evaluating Eurycomanone as a Potential Antiviral Agent Against SARS-CoV-2 Variants

Background SARS-CoV-2 continues to evolve, with new variants showing higher transmissibility and immune evasion. The limited effectiveness of current antiviral drugs highlights the potential of natural product compounds, such as eurycomanone as promising alternatives. Objective This study evaluated the antiviral efficacy of eurycomanone against SARS-CoV-2 variants through experimental and computational analyses. Methods The antiviral activity of eurycomanone was tested in vitro using a cytopathic effect-based assay with Vero E6 cells infected with the original Wuhan-wild-type (WT), Alpha, Delta, and Omicron variants. Cytotoxicity was measured using an ATP-based assay. Computational analysis was performed through molecular docking and dynamics simulations to analyse its binding with SARS-CoV-2 main protease (M pro ) in both WT and Omicron variants. Results Eurycomanone exhibited the strongest antiviral activity against the Omicron variant (EC 50 : 4.58 µM) among all tested variants, with low cytotoxicity (CC 50 > 100 µM) as determined by a cell viability assay in Vero E6 cells. Docking studies revealed strong binding affinities to M pro (WT: −7.7 kcal/mol; Omicron: −8.2 kcal/mol), comparable to nirmatrelvir. Molecular dynamics confirmed stable binding and MMGBSA calculations showed enhanced hydrophobic and electrostatic interactions with the Omicron variant. Conclusion Eurycomanone exhibited notable antiviral activity especially against Omicron, suggesting its potential as a lead compound for developing new antiviral therapies. Further in vivo studies are needed to explore its therapeutic potential.