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

To gain insight into how ATA directly inhibits influenza virus, MDCK cells infected with PR8 and treated with ATA or AH were examined by election microscopy. Compared to untreated PR8-infected cells, or those incubated with AH, ATA treatment was found to induce viral aggregation on the cell surface (Fig. 8) . These findings are similar to previous observations by investiga- tors working with NA inhibitors or NA-defective particles [29, 30] . In these studies, NA was believed to prevent aggregation of progeny viruses on the surfaces of infected cells [29, 31, 32] . Therefore, we postulated that ATA elicits viral aggregation by inhibiting the enzymatic activity of NA. To address this question, we tested the effect of ATA on NA activity and compared it to the effect of NAA, a known NA inhibitor [30] . As expected, NAA inhibited NA activity with very low IC 50 values, while AH showed no inhibition (data not shown). We found ATA inhibited NA activity in a concentration-dependent manner in all viruses, with no marked differences among them. As shown in Fig. 9A , ATA inhibited NA activity from influenza PR8, NC, NY and B viruses with IC 50 s of 7.2 mg/ml, 16.6 mg/ml, 16.4 mg/ml and 6.3 mg/ml, respectively. In addition, ATA significantly inhibited the enzymatic activities of two recombinant NA proteins, N1 and N4 ( Fig. 9B) with IC 50 s of 0.52 mg/ml and 1.0 mg/ml, respectively.