期刊
ANTIVIRAL RESEARCH
卷 200, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2022.105291
关键词
Bourbon virus; Orthomyxoviruses; Emerging zoonotic viruses; Antivirals; Minigenome
资金
- Mayo Clinic internal start up-budget
A highly accessible and robust BRBV minigenome system was developed for high-throughput antiviral drug screening. DHODH inhibitors showed effectiveness against BRBV and other orthomyxoviruses. The system provides a powerful platform for the development of antivirals against emerging orthomyxoviruses.
Bourbon virus (BRBV) is an emerging tick-borne orthomyxovirus that causes severe febrile illness in humans. There are no specific treatments for BRBV disease currently available. Here, we developed a highly accessible and robust, quantitative fluorescence-based BRBV minigenome (MG) system and applied it to high-throughput antiviral drug screening. We demonstrated that human dihydroorotate dehydrogenase (DHODH) inhibitors, hDHODH-IN-4 and brequinar, efficiently reduced BRBV RNA synthesis, and validated these findings using infectious BRBV in vitro. The DHODH inhibitors also exhibited high potency in inhibiting MG activities of other orthomyxoviruses with emerging zoonotic potential, including bat influenza A virus, swine influenza D virus, and Thogoto virus. Our newly developed MG system is a powerful platform for antiviral drug screening across the Orthomyxoviridae family, enabling rapid development and deployment of antivirals against future emerging orthomyxoviruses.
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