The Ottawa Hospital Research Institute

Purpose

The SARs-CoV-2 coronavirus enters cells by binding to its plasma membrane receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 is a member of the renin-angiotensin system that degrades the vasoconstrictor and pro-inflammatory peptide angiotensin II (Ang II) to its vasodilator, anti-inflammatory product Ang-(1-7). This Project involves pre-clinical studies of ACE2-Fc variants with potential therapeutic properties against COVID-19. The compounds will be developed to bind and neutralize the SARs-CoV-2 virus, and to exert intrinsic ACE2 activity, thereby reducing detrimental effects of Ang II. Comprehensive testing of ACE2 enzymatic activity for the designed ACE2-Fc variants arising from this collaboration will be performed. Enzymatic activity testing will be done at three levels: 1. Cell-free assays to test ACE2 enzymatic activity. 2. Cell-based assays using kidney proximal tubular cells. 3. In vivo studies, to determine the effects of lead compounds on blood pressure, kidney injury, and plasma/tissue ACE2 activity in mice with Ang II-mediated hypertension.