Identification of SARS-CoV-2 3CLpro inhibitors from marine actinomycetes through integrated phylogeny-based metabolomics with functional screening and bioinformatic analysis

Researchers have identified promising SARS-CoV-2 3CLpro inhibitors from marine actinomycetes, with extracts from Tubbataha Reefs Natural Park and Nogas Island showing significant inhibitory effects. Among the 75 strains analyzed, 36% exhibited over 90% inhibition, and 27 demonstrated strong potency (IC₅₀ values: 2–8 µg/mL). Phylogenetic analysis linked antiviral activity to specific Streptomyces clades, while metabolomic profiling revealed shared bioactive compounds, including a bicyclic sesquiterpenoid and carbazole alkaloid. Molecular docking confirmed streptocarbazole C's strong binding affinity to the viral enzyme, suggesting potential for development as an antiviral agent. This study integrates phylogeny, metabolomics, and bioinformatics to advance natural product-based drug discovery.

Dalisay, D. S., Mateo, J. C., Teodosio, J. J. R., Jusa, L. M. S., Baladjay, D. M. S., de Guzman, L. S., Balida, L. A. P., & Jamal, J. A. (2025). Identification of SARS-CoV-2 3CLpro inhibitors from marine actinomycetes through integrated phylogeny-based metabolomics with functional screening and bioinformatic analysis. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-25354-0