Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals

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Similarity of microbiome-derived metabolites to synthetic antivirals. 

This brilliant study conducted by Piscotta Frank J. et al. studied the antiviral activity of microbiota derived metabolites on SARS-CoV-2.

Today, the identification of additional antiviral small molecules is essential to complement existing therapies in the COVID-19 pandemic. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored.

In the following study, they used a cell-based SARS-CoV-2 infection assay, to screen culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity.

Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. Those metabolites included: the nucleoside analogue N6-(Δ2-isopentenyl) adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. N6-(Δ2-isopentenyl)adenosine was found to be most potent, it had a 50% inhibitory concentration (IC50) of 2 μM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19.

The exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections.

Stay tuned, such researches and many more are to be presented in the 9th Annual Meeting of the International Society of Microbiota on October 19-21, 2022 - Paris, UNESCO

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