A Novel Ranking System for Identifying Efficacious Anti-Influenza PB2 Inhibitors.

A Novel Ranking System for Identifying Efficacious Anti-Influenza PB2 Inhibitors. Antimicrob Agents Chemother. 2015 Jul 13; Authors: Tsai AW, McNeil CF, Leeman JR, Bennett HB, Nti-Addae K, Huang C, Germann UA, Byrn RA, Berlioz-Seux F, Rijnbrand R, Clark MP, Charifson PS, Jones SM Abstract Through antigenic drift and shift, influenza (flu) viral infections continue to be an annual cause of morbidity in healthy populations and mortality among the elderly and at risk patients. The emergence of highly pathogenic avian influenza viruses like H5N1 and H7N9 and the rapid spread of the swine origin H1N1 influenza virus in 2009 demonstrate the continued need for effective influenza therapeutics. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited start-to-treat window and resistant variants have shown up in the population. In addition, an older class of influenza antiviral drugs, the adamantanes, are no longer recommended for treatment due to widespread resistance.There remains a need for new influenza therapeutics with improved efficacy as well as an expanded window for the initiation of treatment. Azaindole compounds targeting the influenza A virus PB2 protein that demonstrate excellent in vitro and in vivo properties have been identified. To evaluate the vivo efficacy of these PB2 inhibitors, we have utilized a mouse influenza A virus infection model. In add...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research