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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00599887" target="_blank" >RIV/61388963:_____/24:00599887 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/23:00578957

Výsledek na webu

<a href="http://www.ccsss.cz/index.php/ccsss/issue/view/48/87" target="_blank" >http://www.ccsss.cz/index.php/ccsss/issue/view/48/87</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Rift Valley fever virus (RVFV) is a pathogenic arbovirus from the family Phenuiviridae, causing severe disease in both humans and domesticated animals. Outbreaks of this mosquito-borne virus can have devastating effect on the livestock, which exhibit unusual sensitivity to the infection, with possible losses reaching hundreds of millions USD. Currently, there is no approved treatment ot prevention against the human RVFV infections, although attenuated vaccines are available for veterinary use. Nevertheless, their safety and effectivity is dubious. Like other viruses of the former Bunyavirales family (now Elliovirales and Hareavirales), replication mechanism of the RVFV is mediated by its polymerase – the L protein. The 250 kDa large protein is responsible for most of the virus replication and transcription, it contains the endonuclease domain, the RNA-dependent RNA-polymerase domain and the cap-binding domain. This organization is very similar to the linear composition of the heterotrimeric polymerase complex PA-PB1-PB2 of the influenza virus. Similarly to influenza, the process of viral transcription is initiated by a cap-snatching mechanism, during which the host mRNA is cleaved by the L protein endonuclease domain. As the L protein is heavily conserved across the members of the former Bunyavirales family and, although sequentially different, it is structurally and functionally closely similar to the RNA polymerase complex of the influenza A virus, we believe its domains are viable targets for development of novel antivirals.

Název v anglickém jazyce

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

Popis výsledku anglicky

Rift Valley fever virus (RVFV) is a pathogenic arbovirus from the family Phenuiviridae, causing severe disease in both humans and domesticated animals. Outbreaks of this mosquito-borne virus can have devastating effect on the livestock, which exhibit unusual sensitivity to the infection, with possible losses reaching hundreds of millions USD. Currently, there is no approved treatment ot prevention against the human RVFV infections, although attenuated vaccines are available for veterinary use. Nevertheless, their safety and effectivity is dubious. Like other viruses of the former Bunyavirales family (now Elliovirales and Hareavirales), replication mechanism of the RVFV is mediated by its polymerase – the L protein. The 250 kDa large protein is responsible for most of the virus replication and transcription, it contains the endonuclease domain, the RNA-dependent RNA-polymerase domain and the cap-binding domain. This organization is very similar to the linear composition of the heterotrimeric polymerase complex PA-PB1-PB2 of the influenza virus. Similarly to influenza, the process of viral transcription is initiated by a cap-snatching mechanism, during which the host mRNA is cleaved by the L protein endonuclease domain. As the L protein is heavily conserved across the members of the former Bunyavirales family and, although sequentially different, it is structurally and functionally closely similar to the RNA polymerase complex of the influenza A virus, we believe its domains are viable targets for development of novel antivirals.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů