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