14-Deoxy-11,12-dehydroandrographolide exerts anti-influenza A virus activity and inhibits replication of H5N1 virus by restraining nuclear export of viral ribonucleoprotein complexes.

摘要: The highly pathogenic avian influenza H5N1 virus has become a worldwide public health threat, and current antiviral therapies have limited activity against the emerging, resistant viruses. Therefore, effective drugs with novel targets A viruses, strains in particular, should be developed. In present study, 14-deoxy-11,12-dehydroandrographolide (DAP), major component of traditional Chinese medicine Andrographis paniculata, exerted potent anti-influenza A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 A/PR/8/34 (H1N1), A/NanChang/08/2010 (H1N1) A/HuNan/01/2014 (H3N2) vitro. To elucidate underlying mechanisms, series experiments was conducted using (H5N1) as an example. Our results demonstrated that DAP strongly inhibited replication by reducing production viral nucleoprotein (NP) mRNA, NP NS1proteins, whereas had no effect on absorption release towards/from A549 cells. also effectively restrained nuclear export ribonucleoprotein (vRNP) complexes. This inhibitory ought to important anti-H5N1 mechanism DAP. Meanwhile, significantly reduced upregulated expression all tested proinflammatory cytokines (TNF-α, IL-6, IL-8, IFN-α, IL-1β IFN-β) chemokines (CXCL-10 CCL-2) stimulated H5N1. Overall suggest impairs at least part restraining vRNP complexes, inhibition leads subsequent decrease intense cytokine/chemokine expression. turn, modification host excessive immune response may contribute overcoming our knowledge, this study is first reveal anti-inflammatory activities vitro infection.