Computer-Aided Drug Design and Biological Evaluation of Novel Anti-Greek Goat Encephalitis Agents

Abstract

The Flaviviridae family of viruses infects vertebrates and is primarily spread through arthropod vectors. The Greek Goat Encephalitis (GGE) flavivirus belongs to the Flaviviridae family and specifically to the genus Flavivirus. GGE virus, which is endemic in Greece, is the causative agent of tick-borne encephalitis (TBE), an infection of the central nervous system that can be transmitted from animals to humans by ticks. Although, there are very limited data regarding the GGE virus and its epidemiology in Greece, there have been few reported cases of GGE viral infection of goats in northern Greece. However, despite the severity of Flaviviridae causing diseases (e.g. Hepatitis C, Dengue fever, Yellow fever, Classical swine fever, Japanese encephalitis), currently there is not any available anti-flaviviridae therapy. Thus, there is a need for the development of effective anti-GGE viral pharmaceutical strategies. It has been shown that RNA helicases, which are involved in duplex unwinding during viral RNA replication, represent promising antiviral targets. Therefore, we suggest that inhibition of the GGE viral helicase would be an effective approach of interrupting the life cycle of the GGE virus. Our proposed research will be directed towards the computer-aided development of a series of drug-like low molecular weight compounds capable of inhibiting the helicase enzyme of GGE virus. Results derived from a repertoire of multi-disciplinary bioinformatics and statistical methods would enhance our understanding of the mechanism of action of the GGE viral helicase enzyme. Our ultimate goal is to design a series of novel anti-helicase compounds as drug candidates against the endemic GGE virus while the inhibitory activity of our novel compounds will be evaluated biologically.