Partridge et al. determined which human cell line model to use for studying SARS-CoV-2 S protein attachment based off of the mRNA expression of different membrane proteins important to the pathogenesis of COVID-19.  They investigated the following cell types:

- RT4 urinary bladder epithelial cell line
- A549  lung adenocarcinoma alveolar basal epithelial cell line
- Caco2 colorectal adenocarcinoma cell line
- HaCaT skin keratinocyte cell line

RT4 was determined to be the best cell line to use because it expresses both ACE2 and TMPRSS2 which directly interact with SARS-CoV-2 S protein.  It also expresses the following accessory proteins relevant to S protein attachment:

- ADAM17: a metalloprotease that processes ACE2
- rhomboid-like 2 (RHBDL2): a protease that is involved with the function of ADAM17
- CD9: an adaptor protein that controls ADAM17

Cell Lines Developed by Partridge et al. to Study COVID-19

Zhang et al. developed two immortal cell lines from the airway epithelial basal cells of healthy nonsmokers.  The BCi-NS1.1 cell line originated from the large airway epithelium (LAE), and the hSABCi-NS1.1 cell line originated from the small airway epithelium (SAE).  These cells were found to express genes relevant to a SARS-CoV-2 infection, including ACE2 and TMPRSS2.  Furthermore, they are genetically pliable.  Zhang et al. believe that they may be useful for studying the pathogenesis of COVID-19 as well as potential therapeutics.  

Cell Lines Developed by Zhang et al. to Study COVID-19

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

Michigan State University

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

Laboratory Methods in COVID-19 Research

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

Animal Models Used to Study COVID-19

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

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