Meeting report: 30th International Conference on Antiviral Research, in Atlanta, GA, USA

Vere Hodge, R Anthony

Priscilla Yang is investigating the potential of the entry viral glycoprotein (E), mediating attachment and membrane fusion, as a suitable antiviral target for drugs against dengue. It has been confirmed that small molecules can interact with E to give activity in both a target-based assay and a cell culture antiviral assay. The next step is to validate E as an antiviral target in vivo. Although it is necessary to confirm antiviral activity, it is also necessary to show that this approach can lead to antiviral compounds having a high genetic barrier to resistance. It was an encouraging start to find that some compounds did not show resistance up to passage 9. However, I think that Sophie Duraffour holds the record for ICAR's longest resistance test, with resistance to (S)-HPMPDAP appearing in two strains of camelpox virus after passaging 30 times, taking 18 months, before resistant clones could be obtained. (Sophie Duraffour, 22nd ICAR, 3-7 May in Miami Beach, FL, USA). To investigate resistance to dengue, Priscilla's group prepared various dengue mutant viruses containing point substitutions, which were chosen from naturally occurring E sequences identified in public databases. None of the current compounds were active against all these mutant strains. Surely, that suggests that, for these compounds, resistance will be a critical factor to be investigated.