Abstract
Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated.
Published Version
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