What does the role of ACE2 as a receptor for viral entry suggest regarding targeted therapy for COVID-19?
ACE2 (Angiotensin-converting enzyme 2) is upregulated by ACEI, ARBs, and NSAIDs. These cell-bound enzymes also serve as a binding site for the S protein of SARS-CoV-2 virus, facilitating viral entry into cells by endocytosis. This fact raised initial concerns that these therapeutic drugs may increase the risk of COVID-19 infections or severity. However, other data suggests that the presence of ACE2 may have positive effects attributable at least in part to decreased lung injury secondary to increased production of angiotensin-(1-7). Note that ACEI binds to ACE1, not ACE2; ARBs bind to AT1 receptor, not AT2. Additionally, there is theoretical benefit in having increased levels of ACE2 in circulation because they may bind to circulating virions before they gain entry into a host cell. This hypothesis is the basis for current clinical trials evaluating the efficacy of ARBs like losartan for COVID-19 infections (https://clinicaltrials.gov/ct2/show/NCT04335123).
Hochman M, Kim J (eds). Keck School of Medicine of USC COVID-19 Evidence-Based Summary. Last updated May 5, 2020. Accessed May 12, 2020 at: http://keck.usc.edu/wp-content/uploads/2020/05/Evidence-Based-COVID.5-5.pdf
Sparks MA, Hiremath S, et al. The coronavirus conundrum: ACE2 and hypertension edition. NephJC 2020 – last updated May 4, 2020. Accessed May 12, 2020 at: http://www.nephjc.com/news/covidace2