Abstract
Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
Highlights
Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy
NiPT5 inhibits the transcription of IAV viral RNAs (vRNAs) and the expression of IAV NP protein (Fig. 3)
We observed that NiPT5 inhibits type I interferon response but does not sensitize cells to virus infection suggesting that NiPT5 may block viral replication at a step before the detection of virus infection by the host cells
Summary
Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. NiPT5 impedes the signaling cascades that lead to the activation of NF-kB in response to different stimuli, such as LPS and TNFa. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. NiPT5 prevents activation of NF-kB, and IRF3 in response to IAV infection These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication. We previously showed that a Nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) is an anti-inflammation agent by blocking the TNFa- and LPS-induced activation of NF-kB9. We report a simple and safe cell-based screening system for IAV replication inhibitors and demonstrate the potent antiviral effect of NiPT5 against IAV and vesicular stomatitis virus (VSV)
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