During the course of searching for antiviral agents from Chinese medicinal herbs, we found that the supercritical fluid extract (SFE) of Centipeda minima possessed good in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 H1N1 (PR8). Bioassay-guided isolation and identification led to the isolation from this extract of seven pseudoguaianolides (1-7). These, as well as nine other sesquiterpene lactones (8-16) previously isolated from this herb were all tested for their anti-PR8 activity using both the cytopathogenic effect (CPE) reduction and cell counting kit 8 (CCK8) assays. As a result, eight pseudoguaianolides (1-8) possessing an α,β-unsaturated cyclopentenone moiety showed antiviral activity against PR8 to different extents. Of the active compounds, brevilin A (4) exhibited the strongest anti-PR8 activity, with an IC50 value much lower than that of the positive control ribavirin. Mechanistic study revealed that brevilin A affected the intracellular replication of PR8 via downregulating the expression of viral M2 protein. All these results suggest the potential application of the pseudoguaianolides containing an α,β-unsaturated cyclopentenone moiety (e.g. brevilin A) in the treatment of influenza virus infection.
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