SARS-CoV-2 S protein is different than other coronaviruses at amino acid residue position 498. Molecular modeling projections suggest that this difference at position 498 would cause SARS-CoV-2 S protein to not efficiently to bind to the regional binding domain of mACE2. Glutamine 498 was replaced with tyrosine, and proline 499 was replaced with threonine from the WIV1 and SARS-CoV-1 viruses. This led to the creation of the recombinant virus SARS-CoV-2 MA.  Experiments have revealed that this recombinant virus can use murine ACE2 (mACE2) for in vitro infection models, and it does not grow more efficiently than the wild type virus in human cells.  

SARS-CoV-2 MA Recombinant SARS-CoV-2 Virus

It is currently a problem that SARS-CoV-2 will not bind to animal model ACE2 receptor enzymes.  Instead of modifying the host organism, it was proposed that SARS-CoV-2 S protein could be remodeled to effectively bind to murine ACE2 (mACE2).  Recombinant SARS-CoV-2 viruses used to study COVID-19 include:

- SARS-CoV-2 MA

Michigan State University

- Animal models
- Cell lines
- Genetically engineered SARS-CoV-2

Laboratory Methods in COVID-19 Research

Dinnon, K. H., Leist, S. R., Schäfer, A., Edwards, C. E., Martinez, D. R., Montgomery, S. A., ... & Gully, K. L. (2020). A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature, 1-9.
https://www.nature.com/articles/s41586-020-2708-8
doi: 10.1038/s41586-020-2708-8

A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures

- developed by Partridge et al.
- developed by Zhang et al. 

Cell Lines Used to Study COVID-19

While many animals have been used in laboratory studies of SARS-CoV-2, no model has been created that replicates the severity of the disease similar to hospitalized COVID-19 patients. In order to reduce COVID-19 morbidity and mortality, a reliable animal model is necessary to understand the biology of the infection as well as possible interventions. Animal models that produce severe infections, specifically pathogenesis of Covid-19 induced ARDS, are neccesary to develop reliable therapeutics. 

Potential animal models include:

- K18-hACE2 Mice
- AAV-hACE2 Mice
- HFH4-hACE2 Mice
- African Green Monkeys
- Rhesus Macaques

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