Project 467081

Since late 2019, the world is dealing with the coronavirus disease-19 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Causing millions of infection cases and deaths, this pandemic has severely impacted the healthcare and economy sectors, among others. With the continuing viral spread and rising cases, novel variants such as the delta B.1.617.2 have emerged with key mutations in structural proteins, conferring the virus to be more infectious compared to the wild type strain. The rise of SARS-CoV-2 variants with such mutations does also raise the concern of reducing the efficacy of existing vaccines, and this has been reported as breakthrough cases. Further, structural mutations in important viral proteins have also been shown to arise in the context of immunodeficient patients with chronic SARS-CoV-2 infection and receiving treatment. Therefore, one objective of our project is to model the genetic evolution of the virus in vivo on immunodeficient deficient mice in presence of antivirals and SARS-CoV-2 antibodies. Mice susceptible to SARS-CoV-2 and knocked out in the signaling lymphocyte activation molecule (SLAM)-associated protein, SAP (K18-hACE2 transgenic/SAP-/-) will be used to model immunodeficiency. This will be followed by sequencing viral samples obtained from these infected immunodeficient mice at different time points. Doing so will provide a basis of tracking how SARS-CoV-2 evolves genetically in the context of immunodeficiency and treatment which could allow to predict those arising in human immunodeficient patients.