SARS-CoV-2 tropism in the brain and its relationship to COVID-19 pathogenesis

COVID-19 is a US and global disaster which has led to the deaths of almost a million individuals, including over 203,000 Americans, thus far. COVID-19 is caused by a novel beta-coronavirus (CoV) known as Severe Acute Respiratory Syndrome (SARS)-CoV-2, which was reported to cause severe pneumonia and lethal respiratory failure. Little is known about the disease mechanism of this virus and its disease mechanism. In this application, we propose to test the effects of SARS-CoV-2 on the brain. We will develop multiple cell-type specific mouse models that express the SARS-CoV-2 receptor, human ACE2, in a cell-type specific manner. We will then use a variety of molecular, biochemical, histological and neuroscience approaches to test the brain tropism of SARS-CoV-2 in depth and the effects of that on the central regulation of respiration. This proposal will have a transformative impact on our current understanding of COVID- 19 and its mechanisms of pathogenesis and will uncover important therapeutic targets.