Abstract
The coronavirus disease 2019 (COVID-19) is a master killer which appeared suddenly and which has already claimed more than 200,000 human lives. In this situation, laboratories are in urgent need for a COVID-19 murine model to search for effective antiviral compounds. Here we propose a novel strategy for the development of mice that can be inoculated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 causative agent. In humans, two proteins – ACE2 and TMPRSS2 – are involved in SARS-CoV-2 cells entry and, thus, we decided to introduce their genes into a murine genome. These genes will be placed with LoxP sites under the murine Tmprss2 promoter. Such an approach can provide a representative model with the opportunity to control the viral sensitivity of an animal population and tissue specificity of hACE2 and hTMPRSS2 expression.
 Graphical abstract:
 The new COVID-19 model should be based on inducible co-expression of the human ACE2 and TMPRSS2 genes. Activation of ACE2 and TMPRSS2 genes will occur only in the virological laboratory, after crossbreeding with Cre-mice. Before activation, mice will be resistant to SARS-CoV-2 for their biological safety during the pandemic.
Highlights
The COVID-19 outbreak is a dramatic, rapidly evolving situation
To improve the virus inoculation, a few transgenic lines of mice were created with humanized angiotensin-converting enzyme 2 (ACE2) gene
First of all, we consider that mice with two humanized ACE2 and transmembrane protease/serine subfamily member 2 (TMPRSS2) genes will be more sensitive to viral invasion
Summary
The COVID-19 outbreak is a dramatic, rapidly evolving situation. The search for effective approaches to SARS-CoV-2 infection therapy and prevention has become one of the most important tasks for medicine and in the foreseeable future. Soldatov VO et al.: On the way from SARS-CoV-sensitive mice to murine COVID-19 model The new COVID-19 model should be based on inducible co-expression of the human ACE2 and TMPRSS2 genes. Mice are low-sensitive to SARS-CoV infection, but can be poorly inoculated by the virus.
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