How one enzyme is a double-edged sword in the battle against Covid-19
In all the research surrounding COVID-19, one protein stands out: Angiotensin-converting enzyme 2 (ACE-2). The protein has garnered attention in the scientific community because it provides key insights into how Covid-19 infects and damages our cells.
The protein ACE-2 is found on the surfaces of many cells, including those in our heart and lungs. It functions in the Renin-angiotensin-aldosterone system (RAAS), which is a metabolic pathway that handles blood pressure, wound healing, and inflammation (1). ACE-2 works to break down the protein Angiotensin II, which causes inflammation, higher blood pressure, possible damage to blood vessels, difficulty breathing, and can lead to cell death. By breaking down Angiotensin II, the ACE-2 enzyme serves an important function in maintaining bodily health by preventing these symptoms (1).
A similar yet different enzyme is ACE-1. This enzyme creates Angiotensin II and thus counteracts the effects of ACE-2 (1). Many commonly prescribed medicines inhibit the function of ACE-1 such as ACE inhibitors, which are often used by patients with high blood pressure or heart issues. Several studies have suggested that ACE inhibitors use may increase the activity of ACE-2 (2, 3).
Like most enzymes, ACE-2 has a binding site where molecules with the correct shape can attach. When SARS-CoV-2, the virus that causes Covid-19, binds to ACE-2, the enzyme will cut into the cell and bring the virus with it; ACE-2 is the doorway that allows the virus to infect our cells. Moreover, whenever the virus occupies the binding site of the ACE-2 receptor, it inhibits the activity of the enzyme, so ACE-2 cannot break down Angiotensin II (1).
If the ACE inhibitor increases the activity of ACE-2 and SARS-CoV-2 uses ACE-2 to infect cells, then would ACE inhibitors heighten the severity of illness? And should their use be discontinued? So far, many studies oppose both contentions (3). Patients with high blood pressure or other heart issues are already predisposed to more severe infections (4). If their ailments are left untreated, then their condition may worsen when they are infected with Covid-19. Experts and professionals say that there is a “clear potential for harm related to the withdrawal of RAAS inhibitors in patients in otherwise stable condition”(4). For these reasons, many scientists strongly discourage the discontinuation of ACE inhibitors for patients (3).
Lastly, active research surrounding ACE-2 has recently become more prevalent. Researchers at the Louvain Institute have discovered ways to possibly block Sars-Cov-2 from binding with ACE-2. They used tiny proteins that were derived from ACE-2 itself that would take up binding sites on ACE-2, thus reducing the number of cells that SARS-Cov-2 could enter (5). The virus was 76% less likely to bind to ACE-2 enzymes when these proteins were used (5).
The ACE-2 enzyme has captivated the attention of medical researchers around the globe. The enzyme’s role as a cellular doorway for Sars-Cov-2 as well as its ability to regulate blood pressure in the RAAS helps to our understanding of how Covid-19 interacts with our body. Exciting research surrounding ACE-2 is happening, and the next big breakthrough may make use of this enzyme.
– Timothy Guan
- Sriram, K., Insel, P., & Loomba, R. (2020, September 06). What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain. Retrieved October 14, 2020, from https://theconversation.com/what-is-the-ace2-receptor-how-is-it-connected-to-coronavirus-and-why-might-it-be-key-to-treating-covid-19-the-experts-explain-136928
- Liji, T. (2020, April 21). Do ACE inhibitors increase SARS-CoV-2 binding to ACE2? Retrieved October 14, 2020, from https://www.news-medical.net/news/20200420/Do-ACE-inhibitors-increase-SARS-CoV-2-binding-to-ACE2.aspx
- Mehra, M., J., & Rubin, E. (2020, June 18). Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19: NEJM. Retrieved October 14, 2020, from https://www.nejm.org/doi/full/10.1056/NEJMoa2007621
- Vaduganathan, M. (2020, June 11). Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19: NEJM. Retrieved October 14, 2020, from https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?fbclid=IwAR3clnrZDMcN1weWl0JgoqDvMvTDw8-qI_A7-PhdM3rkauTHszqZkLCorfw
- Yang, J., Petitjean, S., Koehler, M., Zhang, Q., Dumitru, A., Chen, W., . . . Alsteens, D. (2020, September 11). Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Retrieved October 14, 2020, from https://www.nature.com/articles/s41467-020-18319-6