Advances in Targeting ACE2 for Developing COVID-19 Therapeutics

Abstract

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.

Mendelian randomization supports causality between COVID-19 and glaucoma

“…[41][42][43] Furthermore, it is verified that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma, [44] at the same time, drugs targeting ACE2 receptors can be considered as therapeutic candidates for COVID-19 treatment. [45,46] However, COVID-19 is thought to be a cause of vascular complications. [47] These findings suggest that endothelial dysfunction, inflammation, cytokine release, hypercoagulability, and hypoxia contribute to the development of thrombosis.…”

Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

“…The severity and susceptibility of COVID‐19 were relevant to the expression level and SNP polymorphism of ACE2 45 . The favorable treatment results in COVID‐19 patients after the treatment of targeting ACE2 expression also indicated the critical role of ACE2 in COVID‐19 46 . However, the role of local immune response and ACE2 expression in the severity of COVID‐19 and cancer risk needs further research to verify.…”

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

“…One area of concern is the interaction of neutralizing antibodies with ACE2, an endogenous protein present on the surface of many human cells. ACE2 plays a crucial role in regulating blood pressure and other physiological processes, and the spike protein of SARS-CoV-2 has a similar structure to ACE2, making it a potential target for neutralizing antibodies (Alfaleh et al, 2022;Eslami et al, 2022;Suvarnapathaki et al, 2022). Nevertheless, several potential ramifications of this interaction are still unresolved.…”