Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases

Hashem, Anwar M.; Flaman, Anathea S.; Farnsworth, Aaron; Brown, Earl G.; Van Domselaar, Gary; He, Runtao; Li, Xuguang

Upon demonstrating that ATA protects MDCK cells from influenza infection by reducing viral replication and release, we sought to investigate the mechanism underlying the anti-influenza activities of ATA. The protection of influenza-infected MDCK cells should be enhanced by simultaneous treatment with two antivirals acting via different mechanisms. Therefore, MDCK cells infected with influenza were treated concomitantly with ATA and an agent with a known antiviral mechanism. As shown in Fig. 5 , the cytopathic effect induced by influenza A viruses in MDCK cells was reduced significantly by concomitant treatment with ATA and AH, compared to either treatment alone. The protective effects of combined ATA and AH treatment were further confirmed by quantitative detection of influenza A viruses present in the culture supernatants by ELISA (Fig. 6) . Notably, cotreatment with ATA and AH virtually abolished H1N1 and H3N2 virus production in the media. Since AH effects its anti-influenza properties by targeting the viral M2 protein to prevent efficient uncoating of incoming viral particles, we concluded that inhibition of influenza replication and release by ATA is mediated by a distinct mechanism.