Advances in Targeting ACE2 for Developing COVID-19 Therapeutics

Since the onset of the coronavirus pandemic in December 2019, the SARS-CoV-2 virus has accounted for over 6.3 million lives resulting in the demand to develop novel therapeutic approaches to target and treat SARS-CoV-2. Improved understanding of viral entry and infection mechanisms has led to identifying different target receptors to mitigate infection in the host. Researchers have been working on identifying and targeting potential therapeutic target receptors utilizing different candidate drugs. Angiotensin-converting enzyme-2 (ACE2) has been known to perform critical functions in maintaining healthy cardiorespiratory function. However, ACE2 also functions as the binding site for the spike protein of SARS-CoV-2, allowing the virus to enter the cells and ensue infection. Therefore, drugs targeting ACE2 receptors can be considered as therapeutic candidates. Strategies targeting the level of ACE2 expression have been investigated and compared to other potential therapeutic targets, such as TMPRSS2, RdRp, and DPP4. This mini review discusses the key therapeutic approaches that target the ACE2 receptor, which is critical to the cellular entry and propagation of the novel SARS-CoV-2. In addition, we summarize the main advantages of ACE2 targeting against alternative approaches for the treatment of COVID-19.