Isolation of Two Antiviral Compounds from Pelargonium Graveolens Displaying Different Modes of Action

This study explores the remarkable dual antiviral potential of Pelargonium graveolens, an edible aromatic plant widely valued in traditional medicine and culinary applications. The ethanol extract from P. graveolens leaves and its ethyl acetate fraction demonstrated significant inhibitory efficacy against both Herpes Simplex Virus Type 2 (HSV-2) and Coxsackievirus B3 (CVB-3), with notable selectivity index of 134 and 83, respectively. Mechanistic investigations revealed distinct modes of action: the ethanol extract primarily targets viral entry processes and exhibits direct virucidal effects against HSV-2, whereas the ethyl acetate fraction specifically inhibits CVB-3 post-infection. Bioassay-guided fractionation and purification using TLC and HPLC-DAD-ESI-MSn led to the identification of two bioactive compounds: quinic acid from the ethanol extract and kaempferol dimethyl ether from the ethyl acetate fraction. Molecular docking analyses yielded results not markedly different from our experimental findings, demonstrating the most favorable interactions between quinic acid and the HSV-2 fusion regulator complex gH-gL, which is crucial for viral entry, as well as between kaempferol dimethyl ether and CVB-3 RNA polymerase. Drug-likeness assessment confirmed both compounds comply with Lipinski's Rule of Five, suggesting favorable pharmacokinetic profiles. The presence of two bioactive compounds within Pelargonium graveolens, each exhibiting distinct antiviral mechanisms against different viruses, highlights the plant as a promising source for the development of novel broad-spectrum antiviral therapeutics.