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

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Eric D Lazartigues
Organization: UNIVERSITY OF NORTH DAKOTA
Fiscal Year: 2021
Award: $642,597
Funding agency: National Heart Lung and Blood Institute

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.

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