tetano
Editor, Senior Moderator
ACS Infect Dis. 2016 Sep 22. [Epub ahead of print]
[h=1]Discovery of Potent Antivirals against Amantadine-Resistant Influenza A Viruses by Targeting the M2-S31N Proton Channel.[/h] Li F[SUP]1[/SUP], Ma C[SUP]1[/SUP], Hu Y[SUP]1[/SUP], Wang Y[SUP]1[/SUP], Wang J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] M2 proton channel; M2-S31N inhibitor; influenza A virus
PMID: 27657178 DOI: 10.1021/acsinfecdis.6b00130
[PubMed - as supplied by publisher]
[h=1]Discovery of Potent Antivirals against Amantadine-Resistant Influenza A Viruses by Targeting the M2-S31N Proton Channel.[/h] Li F[SUP]1[/SUP], Ma C[SUP]1[/SUP], Hu Y[SUP]1[/SUP], Wang Y[SUP]1[/SUP], Wang J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] M2 proton channel; M2-S31N inhibitor; influenza A virus
PMID: 27657178 DOI: 10.1021/acsinfecdis.6b00130
[PubMed - as supplied by publisher]