The role of ACE2 in SARS-CoV-2 infection, pathogenesis, and antiviral interventions

The devastating clinical, psychological, and economic impact of the COVID-9 pandemic, caused by global spread of the second Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), engendered a massive response from the scientific community to rapidly understand the biology of SARS-CoV-2 and to develop interventions to prevent infection or progression to life-threatening disease. Angiotensin converting enzyme-2 (ACE2) and its interaction with the SARS-CoV-2 Spike glycoprotein, which mediates fusion of the virion envelope with the target cell membrane, emerged as a major pharmacological target, as disruption of Spike-ACE2 interaction prevents cells from becoming infected and hence from producing viral progeny. Moreover, the dysregulation of ACE2 that occurs in the context of SARS-CoV-2 infection may have broader implications for COVID-19 pathogenesis. Here we summarize the role of ACE2 as a physiologic regulator of human health, as a facilitator of SARS-CoV-2 infection, as a factor in COVID-19 disease, and as a target for pharmacological interventions. Supplementary Material File (ace-2 review jmv 3-17-25.docx) - Download - 228.54 KB Information & Authors Information Version history Peer review timeline Published Journal of Medical Virology Version of Record5 Dec 2025Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection

Authors Metrics & Citations Metrics Article Usage 245views 104downloads Citations Download citation Michael McVoy, Apparao B. Kummarapurugu. The role of ACE2 in SARS-CoV-2 infection, pathogenesis, and antiviral interventions. Authorea. 18 March 2025. DOI: https://doi.org/10.22541/au.174230482.29404031/v1 DOI: https://doi.org/10.22541/au.174230482.29404031/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.