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Structural and functional characterization of a flaviviral methyltransferase.
Todd, Matthew Zagorey ; Bouřa, Evžen (advisor) ; Honzejková, Karolína (referee)
Genus flavivirus, member of the Flaviviridae family, is a wide-spread group of viral pathogens that pose a global threat to human health. Infections result in neurological and other diseases such as encephalitis, meningitis, microcephaly or haemorrhagic fever with direct anti-viral treatment restricted to only a few members including Yellow Fever Virus (YFV) and Japanese Encephalitis Virus (JEV). The flaviviral genome consists of a positive sense single-strand RNA, translated into a long viral polyprotein cleaved by host and viral proteases into structural and non-structural proteins. Non-structural protein 5 (NS5) is a highly conserved viral protein consisting of a C-terminal RNA-dependent RNA-polymerase (RdRp) and N-terminal methyltransferase (MTase) domain. Flaviviral MTases catalyse the final step of genomic RNA cap formation, that plays a crucial role in viral translation, replication and host immune system evasion. Due to its conservative nature, the flaviviral MTase is a promising drug target. It's structural analysis is needed for the development of broad-spectrum inhibitors and anti-viral treatment. Key words Flavivirus, St. Louis Encephalitis Virus, Flaviviral methyltransferase (MTase), N-7 methylation, 2'-O methylation.
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