Targeted Isolation of Coumarins From Sideritis Species Based on Antiviral Screening and Untargeted Metabolomics

Introduction: The SARS-CoV-2 pandemic has revealed a deficiency in antiviral agents. Plants, traditionally used for respiratory infections, are valuable sources of antiviral compounds. Such a plant is the Sideritis L. taxa (mountain tea), traditionally used against cold and cough. Objectives: Accordingly, this study aimed to investigate the potential protective effects of dichloromethane extracts from Sideritis species against SARS-CoV-2. Materials and Methods Eight Sideritis extracts were tested in an in vitro pretreatment assay to assess the protective effect against SARS-CoV-2. Therefore, infectious virus particles were pre-incubated with the extract, then incubated with Vero E6 cells to finally measure cell viability as a surrogate for virus infection. Untargeted analyses (GC-MS and LC-PDA-HRESIMS) were performed to determine metabolite profiles. Results: Using an orthogonal approach that combines untargeted metabolomics and biological data from a screening assay, we characterized the phytochemical profiles of the different extracts and prioritized samples for targeted isolation. The dichloromethane extract of Sideritis cypria exhibited a notable protective effect. Untargeted analysis revealed coumarins as key compounds, with varying amounts across Sideritis species. Accordingly, fractionation of extract resulted in the isolation of two coumarin derivatives. Structure elucidation was performed using one- and two-dimensional nuclear magnetic resonance experiments. The coumarin, more abundant in S. cypria, demonstrated a slight protective effect in the SARS-CoV-2 pretreatment assay. Conclusion: This study highlights the antiviral effects of Sideritis taxa, although further investigations are necessary to clarify the full potential of the herb. Additionally, the methodology presented herein can serve as a valuable resource for future phytochemical investigations focused on coumarin content within Sideritis genus.