On the way from SARS-CoV-sensitive mice to murine COVID-19 model

Authors

DOI:

https://doi.org/10.3897/rrpharmacology.6.53633

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.

Keywords:

COVID-19, SARS-CoV-2, ACE2, TMPRSS2, mice, CRISPR/Cas9

Author Contribution

Vladislav O. Soldatov, Institute of Gene Biology of the Russian Academy of Sciences; Belgorod State University

Junior researcher of the Core Facility “Genome editing”; junior researcher of the Research Institute of Living Systems Pharmacology.

Marina V. Kubekina, Institute of Gene Biology of the Russian Academy of Sciences

Junior researcher of the Core Facility “Genome editing”.

Yuliya Yu. Silaeva, Institute of Gene Biology of the Russian Academy of Sciences

PhD in Biological Sciences, researcher of the Core Facility “Genome editing”.

Alexandra V. Bruter, Institute of Gene Biology of the Russian Academy of Sciences

PhD in Biological Sciences, researcher of the Core Facility “Genome editing”.

Alexey V. Deykin, Institute of Gene Biology of the Russian Academy of Sciences; Institute of Gene Biology of the Russian Academy of Sciences; Institute of General Pathology and Pathophysiology

PhD in Biological Sciences, Head of the Core Facility and senior researcher of the Center for Precision Genome Editing and Genetic Technologies for Biomedicine; leading researcher of the Laboratory of Pathogenomics and Transcriptomics.

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Published

04-05-2020

How to Cite

Soldatov VO, Kubekina MV, Silaeva YY, Bruter AV, Deykin AV (2020) On the way from SARS-CoV-sensitive mice to murine COVID-19 model. Research Results in Pharmacology 6(2): 1–7. https://doi.org/10.3897/rrpharmacology.6.53633

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Section

Review article

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