Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs

Abstract

Angiotensin-converting enzyme-2 (ACE2) is one of the major components of the renin-angiotensin system (RAS) and participates in the physiological functions of the cardiovascular system and lungs. Recent studies identified ACE2 as the receptor for the S-protein of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and thus acts as the gateway for viral entry into the human body. Virus infection causes an imbalance in the RAS axis and induces acute lungs injury and fibrosis. Various factors regulate ACE2 expression patterns as well as control its epigenetic status at both transcription and translational levels. This review is mainly focused on the impact of environmental toxicants, drugs, endocrine disruptors, and hypoxia as controlling parameters for ACE2 expression and its possible modulation by epigenetic changes which are marked by DNA methylation, histone modifications, and micro-RNAs (miRNAs) profile. Furthermore, we have emphasized on interventions of various phytochemicals and bioactive compounds as epidrugs that regulate ACE2-S-protein interaction and thereby curb viral infection. Since ACE2 is an important component of the RAAS axis and a crucial entry point of SARS-CoV-2, the dynamics of ACE2 expression in response to various extrinsic and intrinsic factors are of contemporary relevance. We have collated updated informations on ACE2 expression modulated by epidrugs, and urge to take over further studies on this important physiological regulators to unravel many more systemic linkages related to both metabolic and infectious diseases, in general and SARS-CoV-2 in particular for further development of targeted interventions.

Biomarkers of ageing and frailty may predict COVID-19 severity

“… Li et al, 2020 ). In addition to the spike protein, ACE2 expression patterns and therefore viral entry potential, are susceptible to epigenetic pressure - a phenomenon involving DNA methylation and histone modifications, whose cumulative effects over the course of a lifetime can profoundly alter ACE2 expression as we age ( Rath et al, 2021 ). This genetic variability of SARS-CoV-2 is likely to disproportionately increase the risk of developing severe disease in older and frail infected, vaccinated, or re-infected individuals.…”

Asthma and COVID-19 Associations: Focus on IgE-Related Immune Pathology

“…In contrast, angiotensin-converting enzyme-2 (ACE2) has been identified as the receptor for the SARS-CoV-2 spike protein that provides the entryway for the virus into host cells [34]. Studies have reported a correlation between increased ACE2 expression and increased infectivity of SARS-CoV-2 [35,36]. Compared to airway cells of patients with non-allergic asthma, cells of patients with allergic asthma show lower ACE2 expression [7].…”

Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures

“…The angiotensin converting enzyme 2 (ACE2) is a part of the renin-angiotensin system and is a major entry point for the SARS-CoV-2 virus [ 17 , 18 , 19 ••, 20 ]. ACE2 is highly expressed in the lung and binds to the spike protein on the SARS-CoV-2 virus, creating a biological vulnerability to infection [ 17 , 18 , 19 ••]. Higher levels of ACE2 expression are correlated with greater susceptibility to SARS-CoV-2 infection and viral loads [ 15 ].…”