Inhibition of influenza A virus replication by resveratrol.

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells, but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins, seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. Different mechanisms might underlie the in vivo efficacy of RV documented in our study, including inhibition of several cell-signaling pathways involved in the inflammatory airway damage that is characteristic of influenza disease. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug, as not only it is more difficult for the virus to adapt to, but it can also be expected to affect viral replication independently of the invader’s type, strain, and antigenic properties.