A nano-luciferase expressing human coronavirus OC43 for countermeasure development

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  • Diefenbacher M.V.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Baric T.J.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Martinez D.R.
    • Other Affiliation: Yale School of Medicine
  • Baric R.S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Catanzaro N.J.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Sheahan T.P.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against novel emerging viruses. Antivirals with broad-spectrum activity overcome this limitation by targeting highly conserved regions or catalytic domains within viral proteins that are essential for replication. For rapid identification of small molecules with broad antiviral activity, assays with viruses representing family-wide genetic diversity are needed. Viruses engineered to express a reporter gene (i.e. luminescence, fluorescence, etc.) can increase the efficiency, sensitivity or precision of drug screening over classical measures of replication like observation of cytopathic effect or measurement of infectious titers. We have previously developed reporter virus systems for multiple other endemic, pandemic, epidemic and enzootic CoV. Human CoV OC43 (HCoV-OC43) is a human endemic CoV that causes respiratory infection with age-related exacerbations of pathogenesis. Here, we describe the development of a novel recombinant HCoV-OC43 reporter virus that expresses nano-luciferase (HCoV-OC43 nLuc), and its potential application for screening of antivirals against CoV.
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  • Article
Rights statement
  • In Copyright
License
  • Attribution-NonCommercial-NoDerivs 4.0 International
Journal title
  • Virus Research
Journal volume
  • 339
Language
  • English
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  • Publisher
Funder
  • Howard Hughes Medical Institute, HHMI
  • NIAID AVIDD, (R01 AI132178, R01 AI132178–04S1, U19AI171292)
ISSN
  • 0168-1702
Publisher
  • Elsevier B.V.

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