Identification of dengue virus inhibitors

Zika, and other members of the Flavivirus genus are major human pathogens for which we lack effective countermeasures. Development of safe and effective vaccines against dengue virus (DENV) has been complicated by the propensity of non-neutralizing antibodies to worsen disease through antibody-dependent enhancement of infection. Antibody responses to the four DENV serotypes and Zika virus (ZIKV) cross-react to a significant extent but do not cross-neutralize. Antibody responses elicited by a vaccine can thus worsen disease upon subsequent infection. Antivirals provide an alternative approach to reduce disease and transmission of DENV and ZIKV. Persistence of ZIKV in immune-privileged sites, as evidenced by detection of ZIKV in semen and saliva for months, represents an additional opportunity for antiviral intervention. We are developing novel assays to identify flavivirus antivirals that act by both established and new mechanisms.