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ID: ALA4382263

Journal: J Nat Prod

Title: Spirostaphylotrichin X from a Marine-Derived Fungus as an Anti-influenza Agent Targeting RNA Polymerase PB2.

Authors: Wang J, Chen F, Liu Y, Liu Y, Li K, Yang X, Liu S, Zhou X, Yang J.

Abstract: A new spirocyclic γ-lactam, named spirostaphylotrichin X (1), and three related known spirostaphylotrichins (2-4) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures were determined by spectroscopic analyses. Spirostaphylotrichin X (1) displayed obvious inhibitory activities against multiple influenza virus strains, with IC50 values from 1.2 to 5.5 μM. Investigation of the mechanism showed that 1 inhibited viral polymerase activity and interfered with the production of progeny viral RNA. Homogeneous time-resolved fluorescence, surface plasmon resonance assays, and a molecular docking study revealed that 1 could inhibit polymerase PB2 protein activity by binding to the highly conserved region of the cap-binding domain of PB2. These results suggest that 1 inhibits the replication of influenza A virus by interfering with the activity of PB2 protein and that 1 represents a new type of potential lead compound for the development of anti-influenza therapeutics.

CiteXplore: 30516983

DOI: 10.1021/acs.jnatprod.8b00656