Epigenetic alterations and genetic variations of angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS-CoV-2: potential clinical implications

Receptor recognition is a crucial step in viral infection and is a critical factor for cell entry and tissue tropism. In several recent studies, angiotensin-converting enzyme 2 (ACE2) has been demonstrated to be the cellular receptor of SARS-CoV-2 as it was previously well known as the receptor of SARS-CoV. SARS-CoV-2 can bind with high affinity to human ACE2 and engages it as an entry receptor. It seems that the genetic, notably epigenetic variations of ACE2 are less known in different populations, indicating the need for its further investigation. These variations have the potential to affect its contribution to the pathogenicity of COVID-19. The contribution of epigenetics in the interindividual variability of ACE2 merits more attention because epigenetic processes can play important roles in ACE2 alterations in various tissues and different people and populations. Analyzing different DNA methylation patterns and microRNAs, contributing to the ACE2 modulation in the lungs will have a high priority. The epigenetic and genetic variations of ACE2 become even more important when considering that some people have mild clinical symptoms despite having COVID-19. The pathogenicity of SARS-CoV-2 infection is complex; therefore, a better understanding of the underlying pathobiology, especially binding the virus to its receptors, could help improve therapeutic and preventive approaches. This review aims to highlight the importance of evaluating both the epigenetic and genetic variations of ACE2 as a receptor for the deadly SARS-CoV-2.