Development of accelerated high-throughput antiviral screening systems for emerging orthomyxoviruses

Satoko Yamaoka, Carla M. Weisend, Vaille A. Swenson, Hideki Ebihara

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number105291
JournalAntiviral Research
StatePublished - Apr 2022


  • Antivirals
  • Bourbon virus
  • Emerging zoonotic viruses
  • Minigenome
  • Orthomyxoviruses

ASJC Scopus subject areas

  • Pharmacology
  • Virology


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