Table 3.

Studies highlighting the role of ACE2 receptor in the pathogenesis of COVID-19

S. no	Author	Study Objective	Finding	References
1	Peng Zhou 2020	Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China	The sequences are almost identical and having sequence identity 79.6% to SARS-CoV. Furthermore, 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. It confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV	[20]
2	Markus Hoffmann 2020	2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option	The serum forms a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention	[90]
3	Tatsuo Hashimoto 2012	Report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections	Results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea	[91]
4	Andrew M. South 2020	Examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19	Role of ACE2 in the progression of SARs-CoV-2 infection and, importantly, whether blockade of the peptidase is an appropriate step, at least acutely and targeted to the pulmonary system rather than systemically. Studies of the multi-faceted roles of the RAAS in the setting of infectious disease is warranted, which should not occur in isolation from the other well-known roles of the system in cardiovascular homeostasis, particularly given the recent focus on the RAAS and the balance of Ang II and Ang-in critical care medicine such as in septic shock	[92]
5	Mahmoud Gheblawi 2020	Recombinant ACE2, gene-delivery of Ace2, Ang 1–7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated RAS (renin-angiotensin system). Recombinant human ACE2 hascompleted clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1–7 levels, respectively	Highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the RAS, together with implications for the COVID-19 pandemic and associated cardiovascular diseases	[93]
6	Yi-Ming Yuan 2015	To explore the role of the Renin–angiotensin–aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke	Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH	[94]
7	Yingxia Liu 2020	The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. Blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity	Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection	[55]
8	Xiaoqiang Chai 2020	Performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes	Finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury	[82]
9	Mei Lin	Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease	Finding suggested that Calcitriol may be regulate the expression of tubular ACE and ACE2 expression	[95]