Abstract
Despite the existence of flu vaccines and small-molecule antiviral drugs, influenza virus infection remains a public health concern that warrants immediate attention. As resistance to the only orally bioavailable drug, oseltamivir, has been continuously reported, there is a clear need to develop the next-generation of anti-influenza drugs. We chose the influenza A virus M2-S31N mutant proton channel as the drug target to address this need as it is one of the most conserved viral proteins and persist in >95% of currently circulating influenza A viruses. In this study, we report the development of a late-stage diversification strategy for the expeditious synthesis of M2-S31N inhibitors. The channel blockage and antiviral activity of the synthesized compounds were tested in two-electrode voltage clamp assays and antiviral assays, respectively. Several M2-S31N inhibitors were identified to have potent M2-S31N channel blockage and micromolar antiviral efficacy against several M2-S31N-containing influenza A viruses.
Original language | English (US) |
---|---|
Pages (from-to) | 726-733 |
Number of pages | 8 |
Journal | ACS Infectious Diseases |
Volume | 2 |
Issue number | 10 |
DOIs | |
State | Published - Oct 14 2016 |
Keywords
- M2 proton channel
- M2-S31N inhibitor
- influenza A virus
ASJC Scopus subject areas
- Infectious Diseases