Abstract
COVID-19 is the newly born pandemic caused by the SARS-CoV-2 virus, which is the recently emerged betacoronavirus that crosses the species barrier. It predominantly infects pneumocytes of the respiratory tract, but due to the presence of angiotensin-converting enzyme II (ACE2) on other cells like surface enterocytes of the upper esophagus and colon, these are also considered as the primary sites of infection. ACE2 receptor served as a cellular entry point for SARS-CoV-2. The expression of the ACE2 receptors is regulated by several factors such as age, tobacco smoking, inflammatory signaling, ACE inhibitors, angiotensin receptor blockers, and comorbidities (chronic obstructive pulmonary disease (COPD), tuberculosis, cerebrovascular disease, coronary heart disease, hypertension, and diabetes). Therefore, scientists are trying to explore the in-depth knowledge of ACE2 and considered it as a potential indirect target for COVID-19 therapeutics. In this focused review, we discussed in detail ACE2 expressions and regulation by different factors in the primary or vulnerable sites of SARS-CoV-2 infections. Clinical trials of rhACE2 in COVID-19 patients are ongoing, and if the outcome of the trials proves positive, it will be a breakthrough for the management of COVID-19. Finally, we suggest that targeting the ACE2 (a master regulator) in a balanced way could serve as a potential option against the management of COVID-19.
Highlights
Since the 21st century, three species of genus β-coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) have crossed the species barrier and caused atypical pneumonia in humans
ACE2 receptors are majorly expressed in epithelial alveolar lining of pneumocyte cells of the respiratory system as well as the upper esophagus, and colon of the gastrointestinal system; these cellular sites are considered as the primary targets of SARS-CoV infection [11, 17, 18]
SARS-CoV-2 is the causative agent of COVID-19, which predominantly infects pneumocytes of the respiratory tract
Summary
Since the 21st century, three species of genus β-coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) have crossed the species barrier and caused atypical pneumonia (severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19) in humans. The SARS and MERS outbreaks were epidemics, while recently, the emerged COVID-19 has become a pandemic. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in December 2019 at Wuhan province in China, spreading across the globe and caused COVID-19. Diarrhea is the early phase of manifestation in coronavirus infections, which is presumably due to viral replication in the Journal of the Renin-Angiotensin-Aldosterone System gastrointestinal tract. In this focused review, we discussed ACE2 expressions in the primary or vulnerable sites of SARS-CoV-2 infections and regulation of ACE2 by a variety of factors such as age, tobacco smoking, inflammatory signaling, ACE inhibitors, angiotensin receptor blockers, and comorbidities
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