Short Lecture "The Hitchhiker’s guide to multi-informative molecular networks: Discovery of anti-SARS-CoV-2 natural compounds"

The heartwood of Pterocarpus santalinus L.f. also known as red sandalwood is traditionally used in Ayurvedic medicine for the treatment of cold-related symptoms [1]. A pigment-depleted heartwood extract (PS-DE) showed promising anti-SARS-CoV-2 activity in Caco-2 cells with an IC₅₀ of 29.9 µg/mL. In order to predict the potential bioactives from the multi-component extract prior to isolation, molecular networking (MN) was performed [2]. Therefore, the extract was fractionated using high-performance counter current chromatography (HPCCC). Eleven generated fractions were tested for anti-SARS-CoV-2 activity and analysed by UPLC-tandem mass (MS²) spectrometry. The MN was generated on GNPS combining the bioactivity data and MS² data. MN analysis indicated that multiple natural compound classes could be responsible for activity and fostered targeted isolation of seven compounds including three new plant metabolites. In total, 15 constituents from the heartwood belonging to pterocarpans and structurally related compounds were tested for anti-SARS-CoV-2 activity. Thereby, two pterocarpans, one isoflavonoid and one stilbene showed distinct antiviral activity (IC₅₀<40 µM) without cytotoxic effects (CC₅₀>100 µM) which corresponds well to the activity of the original extract PS-DE. Based on these findings, a structure-activity relationship (SAR) was established and indicated structural requirements for anti-SARS-CoV-2 activity.

Funding FWF project P 34028

 

MissingLinkText

Conflict of Interest

The authors declare no conflict of interest.

• References

• 1 Dahat Y, Saha P, Mathew JT, Chaudhary SK, Srivastava D.AkKumar. Traditional uses, phytochemistry andpharmacological attributes of Pterocarpus santalinus and future directions: a review. J Ethnopharmacol 2021; 276114127
• 2 Olivon F, Remy S, Grelier G, Apel C, Eydoux C, Guilemot JC, Neyts J, Delang L, Touboul D, Roussi F, Litaudon M.. Antiviral compounds from Codiaum peltatum targeted by a multi-informative molecular networks approach. J Nat Prod 2019; 82 (02) 330-340

Publication History

Article published online:
16 November 2023