Brevilin A, a Sesquiterpene Lactone, Inhibits the Replication of Influenza A Virus In Vitro and In Vivo

Abstract

With the emergence of drug-resistant strains of influenza A viruses (IAV), new antivirals are needed to supplement the existing counter measures against IAV infection. We have previously shown that brevilin A, a sesquiterpene lactone isolated from C. minima, suppresses the infection of influenza A/PR/8/34 (H1N1) in vitro. Here, we further investigate the antiviral activity and mode of action of brevilin A against different IAV subtypes. Brevilin A inhibited the replication of influenza A H1N1, H3N2, and H9N2 viruses in vitro. The suppression effect of brevilin A was observed as early as 4–8 hours post infection (hpi). Furthermore, we determined that brevilin A inhibited viral replication in three aspects, including viral RNA (vRNA) synthesis, expression of viral mRNA, and protein encoded from the M and NS segments, and nuclear export of viral ribonucleoproteins (vRNPs). The anti-IAV activity of brevilin A was further confirmed in mice. A delayed time-to-death with 50% surviving up to 14 days post infection was obtained with brevilin A (at a dose of 25 mg/kg) treated animals compared to the control cohorts. Together, these results are encouraging for the exploration of sesquiterpene lactones with similar structure to brevilin A as potential anti-influenza therapies.