Drug Repurposing Screen Targeting the Endothelial ACE2 for Preventing Cardiovascular Complications in COVID-19 Patients

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Growing clinical evidence shows a significant correlation between the severity of COVID-19 symptoms and the incidence of cardiovascular complications (e.g., heart failure, thrombotic events). It emerges that endothelial dysfunction contributes to the initiation and propagation of acute respiratory failure in severe COVID-19 patients. COVID-19 infects the host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in the vascular endothelium. The binding of the COVID-19 spike protein to ACE2 causes a decrease of cellular ACE2 level.

Reduced ACE2 activity leads to a widespread endothelial dysfunction manifested by enhanced vascular permeability and exacerbated thrombotic events, which take part in the pathology of severe cases of COVID-19 patients. In this proposal, we will develop a high content assay for evaluating endothelial function by measuring the nitric oxide production in human endothelial cells. ACE2 will be knock-downed by siRNA, thus recapitulating clinically the endothelial dysfunction associated with ACE2 downregulation in the severe cases of COVID-19. Using the optimized assay, the team will conduct a high-throughput screen of an FDA-approved drug library to identify candidates that counteract the endothelial dysfunction caused by the ACE2 deficiency. The screen will generate novel drug(s) that can be repurposed to prevent the severe vascular complications in COVID-19 patients.

Lead Principal Investigator (LPI)


Medical Research Centre - Hamad Medical Corporation

Project ID


Total Funding

QAR 67,300 for six months