Aurintricarboxylic acid inhibits influenza virus neuraminidase.
There is a continuing threat that the highly pathogenic avian influenza virus will cause future influenza pandemics. In this study, we screened a library of compounds that are biologically active and structurally diverse for inhibitory activity against influenza neuraminidase (NA). We found that aurintricarboxylic acid (ATA) is a potent inhibitor of NA activity of both group-1 and group-2 influenza viruses with IC(50)s (effective concentration to inhibit NA activity by 50%) values at low micromolar concentrations. ATA was equally potent in inhibiting the NA activity derived from wild-type NA and its H274Y mutant which renders NA resistance to inhibition by oseltamivir. Although ATA is structurally distinct from sialic acid, molecular modeling experiments suggested that ATA binds to NA at the enzyme's substrate binding site. These results indicate that ATA may be a good starting material for the design of a novel class of NA inhibitors for the treatment influenza viruses.
Hung
Hui-Chen
HC
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Tseng
Ching-Ping
CP
Yang
Jinn-Moon
JM
Ju
Yi-Wei
YW
Tseng
Sung-Nain
SN
Chen
Yen-Fu
YF
Chao
Yu-Sheng
YS
Hsieh
Hsing-Pang
HP
Shih
Shin-Ru
SR
Hsu
John T-A
JT
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology*; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D020125:Mutation, Missense; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D053139:Oseltamivir / Q000494:pharmacology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D001312:Aurintricarboxylic Acid; D009439:Neuraminidase