April 20th 2023

Published in Journal of Virology: A new mouse model for preclinical evaluation of potential antivirals

Published in in Journal of Virology: A new mouse model for preclinical evaluation of potential antivirals

As ancestral SARS-CoV-2 viruses are not able to bind to the mouse ACE2 receptor, establishment of SARS-CoV-2 mouse models has been limited to the use of mouse-adapted viruses or genetically modified mice. In parallel, Syrian hamsters are considered one of the best small animal models available for SARS-CoV-2 since SARS-CoV-2 binds efficiently to the hamster ACE2.

Interestingly, some of the variants of concern, such as the Beta B.1.351 variant, show an improved binding to the mouse receptor. The CARE partner KU Leuven (KUL, Belgium) exploited this difference to establish a SARS-CoV-2 Beta B.1.351 variant infection model in an immunodeficient mouse model, i.e., SCID mice, with the aim to develop a robust SARS-CoV-2 mouse infection model for preclinical evaluation of potential antivirals.

The model’s robustness to study the efficacy of small-molecule inhibitors of SARS-CoV-2 infection was confirmed by its sensitivity to molnupiravir or nirmatrelvir and by more efficient replication of the Beta SARS-CoV-2 variant in SCID mice than in wild-type mice.

This SARS-CoV-2 SCID mouse infection model offers an advantage in comparison to other SARS-CoV-2 mouse models – no need to use mouse-adapted virus strains or genetically modified mice – and to the hamster models as it requires lower amounts of drugs, less space, etc..  On the other hand, a limitation is that mice are only susceptible to the Beta variant and that since small-molecule inhibitors should have equipotent activity against all variants, this will be of limited concern for studies with such drugs.

To learn more, click here: A SCID mouse model to evaluate the efficacy of antivirals against SARS-CoV-2 infection