Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2.
血管紧张素转换酶 2: 肾素-血管紧张素系统的SARS-CoV-2 受体和调节因子: 庆祝ace2 发现 20 周年。
- 作者列表："Gheblawi M","Wang K","Viveiros A","Nguyen Q","Zhong JC","Turner AJ","Raizada MK","Grant MB","Oudit GY
:ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. 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 renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.
: ACE 2 (血管紧张素转化酶 2) 具有围绕其三价功能的多种生理作用: 肾素-血管紧张素系统的负调节因子，氨基酸转运的促进因子，和严重急性呼吸综合征冠状病毒传染性非典型肺炎-CoV) 传染性非典型肺炎-CoV-2 受体。ACE2 广泛表达，包括在肺、心血管系统、肠道、肾脏、中枢神经系统和脂肪组织中。ACE2 最近被确定为SARS-CoV-2 受体，是冠状病毒疾病 2019 的感染因子，在免疫、炎症、ACE2 和心血管疾病之间提供了关键联系。虽然也密切进化关系传染性非典型肺炎-CoV，受体结合结构域的传染性非典型肺炎-CoV-2 不同几个关键氨基酸残基，较强的结合亲和性人ACE2 受体，这可能解释了更大致病性传染性非典型肺炎-CoV-2.SARS-CoV-2 结合后ACE2 功能的丧失是由蛋白水解裂解和加工的内吞和激活驱动的。ACE2 系统是对抗射血分数降低和保留的心力衰竭 (包括心肌梗死和高血压) 以及对抗肺病和糖尿病的关键保护途径。ACE2 控制肠道微生态失调和血管通透性已成为肺动脉高压和糖尿病心血管并发症的重要机制。重组ACE2，Ace2 、Ang 1-7 类似物和Mas受体激动剂的基因递送增强ACE2 作用，作为与激活的肾素-血管紧张素系统相关的疾病的潜在疗法。rhACE2 (重组人ACE2) 已完成临床试验，分别有效降低或增加血浆血管紧张素II和血管紧张素 1-7 水平。我们的综述总结了过去 20 年的进展，强调了ACE2 作为新型SARS-CoV-2 受体和肾素-血管紧张素系统负调控因子的关键作用，以及对冠状病毒疾病 2019 大流行和相关心血管疾病的影响。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.