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

Since inhibition of influenza by ATA and AH is mediated by two distinct mechanisms, it is not surprising that we observed additive effects upon simultaneous treatment with both compounds. Recently the Advisory Committee on Immunization Practices (ACIP) recommended against the use of amantadine or rimantidine to treat influenza infection [34] due to increasing evolution of M2 blocker-resistant influenza strains [14, 15] . Although influenza strains resistant to NA inhibitors are less prevalent [5] , resistance to oseltamivir has also been reported [15, 46] . This suggests that the use of a single class of antiviral may have limited protective value and future influenza treatment strategies will likely include combinations of medications. Notably, combined used of both M2 blockers and NA inhibitors does provide additive protection against influenza infection compared to either treatment alone [26, 47] . Mice infected with 50% lethal doses of either amantadinesensitive or amantadine-resistant H5N1 influenza, were more protected by co-treatment with amantadine and oseltamivir than those treated with one drug only [47] . We found that simultaneous treatment with ATA and AH significantly protected MDCK cells from influenza and dramatically reduced the abundance of influenza particles released in the medium.