The betacoronavirus SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that has led to a public health emergency and social disruption on a scale not seen since the influenza pandemic of 1918. This new human pathogen is genetically, antigenically and phenotypically distinct from coronaviruses that circulate seasonally in humans and cause symptoms of the common cold. SARS-CoV-2 therefore presents many unknowns. To contribute to what we hope will be a broad effort on the part of the global infectious diseases community, we propose herein to generate critical reagents that will facilitate research efforts and accelerate progress toward filling critical knowledge gaps. Namely, we propose the construction of an infectious molecular clone of the GA-83E strain of SARS-CoV-2 and derivatives thereof expressing fluorescent and luciferase-based reporter genes. An infectious molecular clone, or reverse genetics system, is an extremely powerful tool which allows the generation of viral variants carrying targeted mutations. This capability will accelerate progress toward critical research goals. For example, the use of variant viruses carrying reporter genes can greatly streamline identification of small molecule inhibitors and the titration of immune sera and monoclonal antibodies. Similarly, the ability to introduce targeted mutations is invaluable in efforts to map antigenic sites, identify escape mutations, map determinants of transmission and virulence, and identify viral features important for zoonotic potential. In sum, the reagent- generation effort outlined herein is designed to rapidly furnish the emerging SARS-CoV-2 field with an essential tool of modern virology.
SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that has led to a public health emergency and social disruption on a scale not seen since the influenza pandemic of 1918. To contribute to the research response to the pandemic, we will generate critical reagents that will accelerate progress toward improved diagnostics, countermeasures and understanding of the potential for similar emergence events to occur in the future.
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