Antiviral activity of ST081006 against the dengue virus

Abstract

Dengue virus, the causative agent for the dengue fever, infects approximately 50–100 million people worldwide per year. The high incidence of dengue fever, along with its potential to develop into a severe, life-threatening form, resulted in great interest in the discovery of an antiviral against it. In this study, we constructed a DENV2-EGFP infectious clone, established a fluorescence-based, high-throughput screening platform, and conducted a screen for anti-DENV compounds on a flavonoid-derivative library, Amongst the hits identified, ST081006 was found to be a strong inhibitor of the DENV replication. Time-course studies suggest that the presence of ST081006 is necessary to inhibit successive rounds of virus replication. Further investigations demonstrated that ST081006 affects the synthesis of both viral protein and viral RNA, and one anti-DENV mechanism is the direct inhibition of viral protein synthesis. The replication of all dengue serotypes, along with that of the enterovirus EV-A71, was shown to be affected by ST081006. Attempts to generate ST081006-resistant DENV were unsuccessful, and thus hints at host factors as potential drug target. Together, these results suggest that ST081006 affect DENV replication, likely by acting on a target involved in the viral protein and/or RNA synthesis pathway.