Structural and functional insights in flavivirus NS5 proteins gained by the structure of Ntaya virus polymerase and methyltransferase.

0586989 - ÚOCHB 2025 RIV US eng J - Článek v odborném periodiku
Krejčová, Kateřina - Krafčíková, Petra - Klíma, Martin - Chalupská, Dominika - Chalupský, Karel - Žilecká, Eva - Bouřa, Evžen
Structural and functional insights in flavivirus NS5 proteins gained by the structure of Ntaya virus polymerase and methyltransferase.
Structure. (2024). ISSN 0969-2126. E-ISSN 1878-4186
Grant CEP: GA ČR(CZ) GA21-25280S; GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:61388963
Impakt faktor: 5.7, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1016/j.str.2024.04.020

Flaviviruses are single-stranded positive-sense RNA (+RNA) viruses that are responsible for several (re)emerging diseases such as yellow, dengue, or West Nile fevers. The Zika epidemic highlighted their dangerousness when a relatively benign virus known since the 1950s turned into a deadly pathogen. The central protein for their replication is NS5 (non-structural protein 5), which is composed of the N-terminal methyltransferase (MTase) domain and the C-terminal RNA-dependent RNA-polymerase (RdRp) domain. It is responsible for both RNA replication and installation of the 5' RNA cap. We structurally and biochemically analyzed the Ntaya virus MTase and RdRp domains and we compared their properties to other flaviviral NS5s. The enzymatic centers are well conserved across Flaviviridae, suggesting that the development of drugs targeting all flaviviruses is feasible. However, the enzymatic activities of the isolated proteins were significantly different for the MTase domains.
Trvalý link: https://hdl.handle.net/11104/0354315