A cell-based screening system for anti-influenza A virus agents

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.

Identification of 5-Methoxy-2-(Diformylmethylidene)-3,3-Dimethylindole as an Anti-Influenza A Virus Agent

“…Four new synthetic indole derivatives (Fig 1A) were tested for antiviral activity using a cell-based screening system for IAV replication inhibitors[11]. A non-replicative PR8 strain IAV carrying eGFP in place of the PB1 gene (PR8-PB1flank-eGFP) was used to infect A549 cells that stably express PB1 protein (A549-PB1).…”

“…However, the rise of drug resistance strains has become a big challenge for efficient antiviral therapy. We have previously described a cell-based screening system for identifying inhibitors of IAV replication[11]. In this study, we used this screening system to test four novel synthetic indole derivative agents (named in short 525A, 526A, 527A and 528A) for their anti-influenza A virus activities.…”