Russia creates its own humanized mice to test COVID-19 vaccines and drugs

May 04, 2020

Following the recent Coronavirus outbreak, almost three million people have been infected worldwide, whereas the death toll has already passed the 200,000 mark, according to official reports. Meanwhile, a vaccine remains to be found, and classic medications show low efficacy. Under these conditions, it is up to pharmacologists to do their best in the search of novel treatments. However, laboratory studies are limited by the absence of COVID-19 animal models.

Russian scientists from the Institute of Gene Biology of the Russian Academy of Sciences, the State Virology and Biotechnology Research Center "Vector" and Belgorod University are already working on the development of SARS-CoV-2-sensitive mice to be used as a murine model in tests of potential COVID-19 vaccines and drugs, reports the Office of the Chief State Sanitary Inspector.

To create such a line of mice, researchers have formulated a two-step concept, recently described in the open-access, peer-reviewed scholarly journal Research Results and Pharmacology. Firstly, the mice are to be made biologically safe for routine laboratory practice. Secondly, in order for the mice to be efficient for non-clinical trials, they will need to experience symptoms and pathogenesis as human-like as possible. The scientists believe that they have everything necessary to implement this conception and expect the first results as early as June 2020.

"SARS-CoV-2-inoculated mice will have a human-like pathogenesis and symptoms of the COVID-19. The key difference between a new model and the existing ones will be its biological safety - animals will become sensitive to SARS-CoV-2 only after activation in conditions of a virological laboratory. It makes it possible to nullify the contagion risk for the staff working in nurseries and non-specialised laboratories during a pandemic," the team explains.

Already available data shows that there are two key proteins in the human cells, which are involved in the virus entry. First of all, it is the angiotensin-converting enzyme 2 (ACE2), which is the direct and main target of the coronavirus' "corona". Three lines of transgenic mice with the human ACE2 variant have been found to be susceptible to the SARS-CoV, a causative agent of the SARS outbreak in 2003. However, it was shown that, in addition to ACE2, a molecular pathway of coronavirus invasion contains another important link: the enzyme transmembrane protease serine 2 (TMPRSS2). The blocking of TMPRSS2 prevents SARS-CoV-2 entry on the cell culture in vitro.

To obtain mice with human-like COVID-19 symptoms and pathology, the researchers will introduce human ACE2 and TMPRSS2 genes into the murine genome under the mice's own Tmprss2 promoter. Another key decision on the way of creating the new model is to ensure that SARS-CoV-2 sensitivity is inducible only after the introduction of LoxP sites in front of the human ACE2 and TMPRSS2 genes. As a result, human genes in a murine genome will turn on once a crossbreeding with mice expressing Cre-recombinase occurs.

"The main trick here is that this crossbreed will only happen in specialised virological laboratories, which will prevent the novel line of mice from becoming an infection 'reservoir' in ordinary laboratories," say the researchers.
-end-
Original source:

Soldatov VO, Kubekina MV, Silaeva YuYu, 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

Pensoft Publishers

Related Genes Articles from Brightsurf:

Are male genes from Mars, female genes from Venus?
In a new paper in the PERSPECTIVES section of the journal Science, Melissa Wilson reviews current research into patterns of sex differences in gene expression across the genome, and highlights sampling biases in the human populations included in such studies.

New alcohol genes uncovered
Do you have what is known as problematic alcohol use?

How status sticks to genes
Life at the bottom of the social ladder may have long-term health effects that even upward mobility can't undo, according to new research in monkeys.

Symphony of genes
One of the most exciting discoveries in genome research was that the last common ancestor of all multicellular animals already possessed an extremely complex genome.

New genes out of nothing
One key question in evolutionary biology is how novel genes arise and develop.

Good genes
A team of scientists from NAU, Arizona State University, the University of Groningen in the Netherlands, the Center for Coastal Studies in Massachusetts and nine other institutions worldwide to study potential cancer suppression mechanisms in cetaceans, the mammalian group that includes whales, dolphins and porpoises.

How lifestyle affects our genes
In the past decade, knowledge of how lifestyle affects our genes, a research field called epigenetics, has grown exponentially.

Genes that regulate how much we dream
Sleep is known to allow animals to re-energize themselves and consolidate memories.

The genes are not to blame
Individualized dietary recommendations based on genetic information are currently a popular trend.

Timing is everything, to our genes
Salk scientists discover critical gene activity follows a biological clock, affecting diseases of the brain and body.

Read More: Genes News and Genes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.