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

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

Louis Papageorgiou (Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Athens, Greece), Dimitrios Vlachakis (Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Athens, Greece), Vassiliki Lila Koumandou (Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Athens, Greece), Nikitas Papangelopoulos (Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Athens, Greece) and Sophia Kossida (Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Athens, Greece)
DOI: 10.4018/ijsbbt.2013100101
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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.
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Introduction

Greek Goat Encephalitis (GGE) virus was discovered as an endemic virus species in Greece. Todate, there are very limited data regarding GGE virus and its epidemiology. For the first time it was isolated in 1969 in northern Greece from the central nervous system of a newborn goat with neurological symptoms (Pavlidou, Gerou, Diza, Antoniadis, & Papa, 2008). Symptoms, found in infected animals, associate GGE with the Mammalian tick-borne virus group (Table 1). Taxonomically GGE belongs to the Flaviviridae family, specifically in the genus Flavivirus.

Table 1.
Mammalian tick-bomeFlavivirusgroup (Gould, 2008; Grard et al., 2007; Gritsun et al., 2003).
Virus nameAbbreviationPrincipal tick vectorGeographical distribution
Tick-borne encephalitis virus(European subtype)TBEV-EuI. ricinusCentral/western Europe,
Scandinavia, Korea
Tick-borne encephalitis virus(Siberian subtype)TBEV-SibI. persulcatusRussia, Finland
Tick-borne encephalitis virus(far-eastern subtype)TBEV-FeI. persulcatusRussia, East (China, Japan)
Louping ill virusLIVI. ricinusUK, Ireland, Norway
Spanish sheep encephalomyelitis virusSSEVI. ricinusSpain
Turkish sheep encephalitis virusTSEVI. ricinusTurkey
Greek goat encephalitis virusGGEVI. ricinusGreece
Powassan virusPOWVIxodescookei,
Ixodesmarxi
USA, Canada, Eastern Russia
Kadam virusKADVRhipicephaluspravusUganda, Saudi Arabia
Omsk hemorrhagic fever virusOHFVDermacentorreticulatus (Dermacentormarginatus)Western Siberia
Kyasanur Forest disease virusKFDVHaemaphysalisspinigera (Ixodes spp., Dermacentor spp., Haemaphysalis spp.)India
Alkhurmahemorrhagic fever virusAHFVOrnithodorussavignyiSaudi Arabia
Langat virusLGTVIxodesgranulatusMalaysia, Thailand, Siberia
Karshi virusKSIVOrnithodoruspapillipesUzbekistan
Royal Farm virusRFVArgashermanniAfghanistan
Gadgets Gully virusGGYVIxodesuriaeMacquarie Island

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