Unlocking the Secrets of Orthonairoviral Endonucleases: Synthesis and Evaluation of Innovative Inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F24%3A10483073" target="_blank" >RIV/00216208:11310/24:10483073 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Unlocking the Secrets of Orthonairoviral Endonucleases: Synthesis and Evaluation of Innovative Inhibitors

Popis výsledku v původním jazyce

Orthonairoviruses (Nairoviridae family) are a group of RNA viruses belonging to the Bunyavirales order and are primarily transmitted to humans through ticks and other arthropods. These viruses are responsible for causing a variety of diseases in humans and animals, with symptoms ranging from mild flu-like illness to severe hemorrhagic fever.1 Examples of these orthonairoviruses include CCHFV and YEZV.Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly virulent nairovirus that causes hemorrhagic fever, a severe and often fatal disease in humans with mortality up to 30%. This virus is primarily transmitted to humans through ticks and can also be spread through contact with the blood or bodily fluids.2 CCHFV is known for its rapid onset of symptoms, which can include high fever, severe bleeding, and organ failure3.Yezo virus (YEZV) were recently reported4 as causative agents of febrile illness in China and Japan and distant from known orthonairovirus pathogens, such as Crimean-CCHFV. Both YEZV and CCHFV represent a significant public health concern in regions where it is endemic, such as parts of Africa, Asia, and Europe3,5.Biological studies revealed that nairoviral RNA-dependent RNA polymerase (RdRp) contains endonuclease6 site occupied by Mn2+ ions therefore any inhibitor designed to interfere with the active site must be able to chelate these ions efficiently.Herein, we prepared set of 11 inhibitors with dihydroxypicolinic acid motif which are easily available via four-steps synthesis (Scheme 1). Promising results concerning antiviral activity were obtained through the Thermal Shift assay.

Název v anglickém jazyce

Unlocking the Secrets of Orthonairoviral Endonucleases: Synthesis and Evaluation of Innovative Inhibitors

Popis výsledku anglicky

Orthonairoviruses (Nairoviridae family) are a group of RNA viruses belonging to the Bunyavirales order and are primarily transmitted to humans through ticks and other arthropods. These viruses are responsible for causing a variety of diseases in humans and animals, with symptoms ranging from mild flu-like illness to severe hemorrhagic fever.1 Examples of these orthonairoviruses include CCHFV and YEZV.Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly virulent nairovirus that causes hemorrhagic fever, a severe and often fatal disease in humans with mortality up to 30%. This virus is primarily transmitted to humans through ticks and can also be spread through contact with the blood or bodily fluids.2 CCHFV is known for its rapid onset of symptoms, which can include high fever, severe bleeding, and organ failure3.Yezo virus (YEZV) were recently reported4 as causative agents of febrile illness in China and Japan and distant from known orthonairovirus pathogens, such as Crimean-CCHFV. Both YEZV and CCHFV represent a significant public health concern in regions where it is endemic, such as parts of Africa, Asia, and Europe3,5.Biological studies revealed that nairoviral RNA-dependent RNA polymerase (RdRp) contains endonuclease6 site occupied by Mn2+ ions therefore any inhibitor designed to interfere with the active site must be able to chelate these ions efficiently.Herein, we prepared set of 11 inhibitors with dihydroxypicolinic acid motif which are easily available via four-steps synthesis (Scheme 1). Promising results concerning antiviral activity were obtained through the Thermal Shift assay.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>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