Host dependence of influenza A virus reassortment

The betacoronavirus SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemicthat has led to a public health emergency and social disruption on a scale not seen since theinfluenza pandemic of 1918. This new human pathogen is genetically, antigenically andphenotypically distinct from coronaviruses that circulate seasonally in humans and causesymptoms of the common cold. SARS-CoV-2 therefore presents many unknowns. To contributeto what we hope will be a broad effort on the part of the global infectious diseases community, wepropose herein to generate critical reagents that will facilitate research efforts and accelerateprogress toward filling critical knowledge gaps. Namely, we propose the construction of aninfectious molecular clone of the GA-83E strain of SARS-CoV-2 and derivatives thereofexpressing fluorescent and luciferase-based reporter genes. An infectious molecular clone, orreverse genetics system, is an extremely powerful tool which allows the generation of viralvariants carrying targeted mutations. This capability will accelerate progress toward criticalresearch goals. For example, the use of variant viruses carrying reporter genes can greatlystreamline identification of small molecule inhibitors and the titration of immune sera andmonoclonal antibodies. Similarly, the ability to introduce targeted mutations is invaluable in effortsto map antigenic sites, identify escape mutations, map determinants of transmission andvirulence, 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 fieldwith an essential tool of modern virology.