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

The influenza virus is highly contagious and results in significant morbidity and mortality [2, 34] . While mass vaccination of a susceptible population is the best approach to prevent influenza infections, propensity for mutation and gene reassortment can result in an occasional emergence of novel and unpredicted influenza virus strains. This can give rise to a global influenza pandemic, such as the current triple reassortant swine-origin H1N1 influenza virus [4, 35] . Since considerable time is required to develop and distribute vaccines, novel influenza strains can rapidly spread globally before a vaccine is available for mass immunization. Given the potential for widespread influenza infection, it is crucial to understand and improve treatments for this disease. Antiviral drugs currently in use (such as the M2 blockers amantadine and rimantidine and NA inhibitors oseltamivir and zanamivir) can reduce the duration of flu symptoms. However, a single mutation can render influenza viruses resistant to antiviral drugs such as M2 blockers or NA inhibitors [36] and drugresistant influenza strains have been isolated from patients receiving antiviral treatment [15, 16, [37] [38] [39] . These findings necessitate the exploration of novel anti-influenza agents. We [21, 22] and others [17, 19, 20] have observed that ATA can inhibit a variety of viruses. These observations prompted us to determine the effects of ATA on the replication of influenza virus. In this report, we present data that clearly demonstrates that ATA protects MDCK cells from infection with H1N1 and H3N2 influenza A strains. Specifically, RT-PCR and ELISA analyses indicated that ATA treatment both reduced the intracellular accumulation of viral genomes and the release of influenza viruses into the media. The magnitude of inhibition, as determined by the production of infectious viral particles, was found to be at least 3 logs compared to 1-2 log reduction by either NAA or AH (Table 1) .