LAUSR

Abstract Development of anti‐influenza A virus (IAV) drugs with novel targets and low toxicity is critical for preparedness against influenza outbreaks. In the current study, our results indicated that the novel polyketide compound purpurquinone B (PPQ‐B) derived from acid‐tolerant fungus Penicillium purpurogenum strain JS03‐21 suppressed the replication of IAV in vitro with low toxicity, and may block some stages after virus adsorption. PPQ‐B could inhibit H1N1 (A/Puerto Rico/8/34; PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009) virus replication in vitro, suggesting that PPQ‐B possesses broad‐spectrum anti‐IAV activities. PPQ‐B's antiviral activity may be largely related to its inhibition of some steps that occur 0–4 h after adsorption. Oral administration of PPQ‐B could decrease pulmonary viral titers and improve survival rate in IAV infected mice. PPQ‐B also significantly decreased the production of inflammatory factors TNF‐&agr;, IL‐6, RANTES and KC in IAV infected lungs and A549 cells, suggesting that PPQ‐B may also attenuate the inflammatory responses caused by IAV infection. PPQ‐B may down‐regulate the NF‐&kgr;B and MAPK pathways to inhibit both virus replication and inflammatory responses. In summary, PPQ‐B has the potential to be developed into a novel anti‐IAV drug targeting host EGFR pathway in the future. HighlightsPPQ‐B suppressed IAV replication in vitro with low toxicity, and possessed broad‐spectrum anti‐IAV activities.PPQ‐B's antiviral activity may be largely related to its inhibition of some steps that occur 0–4 h after adsorption.Oral administration of PPQ‐B decreased pulmonary viral titers and improved survival rate in IAV infected mice.PPQ‐B may down‐regulate NF‐&kgr;B and MAPK signaling pathways to inhibit virus replication.