Identification and characterization of polymerase inhibitors of L-protein of Rift Valley fever virus

0578957 - ÚOCHB 2024 RIV CZ eng A - Abstract
Král, Michal - Kotačka, Tomáš - Radilová, Kateřina - Gregor, Jiří - Machara, Aleš - Reiberger, Róbert - Kožíšek, Milan
Identification and characterization of polymerase inhibitors of L-protein of Rift Valley fever virus.
Czech Chemical Society Symposium Series. Roč. 21, č. 5 (2023), s. 183. ISSN 2336-7202.
[Annual meeting of the National Institute of Virology and Bacteriology (NIVB) /2./. 02.10.2023-05.10.2023, Kutná Hora]
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388963
Keywords : Rift Valley fever virus * L-protein * polymerase inhibitors
OECD category: Virology
http://www.ccsss.cz/index.php/ccsss/issue/view/41/75

Rift Valley fever virus (RVFV) is a mosquito borne, pathogenic phlebovirus of the order Bunyavirales, causing severe disease in both humans and domesticated animals. Outbreaks of the Rift Valley Fever can have devastating impact on the economy of the affected countries, as the virus can cause immense losses of livestock estimated in hundreds of millions USD. Currently, no approved, specific treatment is available for the RVFV infections. Several vaccine types are available, although they are not widely used, and their actual efficiency and safety is questionable. Like other viruses of the Bunyavirales family, replication mechanism of the RVFV is mediated by the L protein. The 250 kDa large protein is responsible for most of the virus replication, it contains the endonuclease domain, the RNA-dependent RNA-polymerase domain and the cap-binding domain. This organization corresponds to the linear composition of the heterotrimeric complex PA-PB1-PB2 of the influenza3. The process of virus replication is initiated by a cap-snatching mechanism, during which the host mRNA is cleaved by the L protein endonuclease domain. The L protein is heavily conserved across the members of the virus family and, although sequentially different it is structurally and functionally closely similar to the RNA polymerase complex of the influenza A virus.
Permanent Link: https://hdl.handle.net/11104/0347857