Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has currently spread worldwide, leading to high morbidity and mortality. As the putative receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) is widely distributed in various tissues and organs of the human body. Simultaneously, ACE2 acts as the physiological counterbalance of ACE providing homeostatic regulation of circulating angiotensin II levels. Given that some ACE2 variants are known to cause an increase in the ligand-receptor affinity, their roles in acquisition, progression and severity of COVID-19 disease have aroused widespread concerns. Therefore, we summarized the latest literature and explored how ACE2 variants and epigenetic factors influence an individual’s susceptibility to SARS-CoV-2 infection and disease outcome in aspects of ethnicity, gender and age. Meanwhile, the possible mechanisms for these phenomena were discussed. Notably, recombinant human ACE2 and ACE2-derived peptides may have special benefits for combating SARS-CoV-2 variants and further studies are warranted to confirm their effects in later stages of the disease process. As the uncertainty regarding the severity and transmissibility of disease rises, a more in-depth understanding of the host genetics and functional characteristics of ACE2 variants will not only help explain individual clinical differences of the disease, but also contribute to providing effective measures to develop solutions and manage future outbreaks of SARS-CoV-2.
Highlights
Coronavirus disease 2019 (COVID-19) poses a tremendous threat to human health
We explored how angiotensin-converting enzyme 2 (ACE2) variants and epigenetic factors influence an individual’s susceptibility to SARS-CoV-2 infection and disease outcome in aspects of ethnicity, gender and age, and discussed some ACE2-based COVID-19 treatments (Figure 2)
In terms of affinity of the ACE2 variant to the S1 protein, current findings are controversial among studies, and the results lack validation by systems biology studies even though some variants have been believed to enhance the affinity in several reports
Summary
Coronavirus disease 2019 (COVID-19) poses a tremendous threat to human health. As of 4 August 2021, the infection has its presence around the globe with over 199 million of the world population being infected and has claimed over 4 million lives and counting (WHO, 2021). This review provides an update on the possible role of ACE2 variants in both the susceptibility of people to SARS-CoV-2 infection and the outcome of COVID-19. Utilizing 5 fast structure-based computational approaches, HadiAlijanvand and Rouhani (2020) reported the predicted affinities of 240 mutated versions of ACE2 with the SARS-CoV-2 Spike protein, and there were varying degrees of difference in these prediction results.
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