3-anhydro-6-hydroxy-ophiobolin A inhibits the replication of influenza A virus in vitro and in vivo

Influenza is a major cause of morbidity and mortality worldwide, and the emerging drug resistance poses an increasing challenge to the treatment of influenza virus infection. Therefore, the development of a novel antiviral drugs has become an urgent task to combat against the influenza viruses that are resistant to the current therapeutic treatment. Here, by screening a small molecule chemical compound library, we identified 3-anhydro-6-epi-ophiobolin A (named L435) as a potent anti-influenza agent. Mechanistically, L435 markedly reduced influenza virus replication in vitro and in vivo. Importantly, L435 treatment improved the survival of influenza-virus-infected mice, suggesting that L435 may be a novel therapeutic agent for treatment of influenza virus infections. This microarray experiment was carried out to explore gene expression changes in influenza-virus-infected A549 cells after L435 treatment, and find out why L435 could inhibit the replication of influenza A virus. Total RNAs were extracted from three different groups of A549 cells that were mock treated, or infected with WSN and treated with DMSO for 12h, or infected with WSN and treated with L435 for 12 h, using TRIzol reagent (Invitrogen, Carlsbad, CA). Three independent experiments were performed. Samples were amplified and labeled using the One-Color Quick Amp Labeling Kit (Agilent p/n 5190-2305).