血管紧张素转换酶2在新型冠状病毒感染及治疗中的作用概述

摘要：血管紧张素转换酶2(ACE2)是肾素-血管紧张素系统(RAS)重要的组成部分,能够下调RAS,具有抗炎、抗纤维化等作用。同时ACE2还是新型冠状病毒(SARS-CoV-2)的受体,与SARS-CoV-2感染及感染后的临床表现密切相关。血管紧张素转化酶抑制药/血管紧张素Ⅱ受体阻断药(ACEI/ARB)在SARS-CoV-2感染中的作用,目前研究尚有争议。本文对ACE2及ACEI/ARB类药物在SARS-CoV-2感染中的作用作一综述。基于目前的研究证据,建议感染前已使用ACEI/ARB类药物的新型冠状病毒肺炎(COVID-19)患者继续用药,但目前尚不建议将ACEI/ARB类药物用于COVID-19患者的治疗。     

ACE2与新型冠状病毒肺炎的心肾损伤

由新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)不仅可以诱发典型的呼吸系统疾病,也能导致心肾系统等相关疾病。SARS-CoV-2的受体为血管紧张素转换酶2(Angiotensin-converting enzyme 2,ACE2)。本文通过阐述ACE2在心脏和肾脏中的作用,分析SARS-CoV-2感染引起患者心肾损伤的可能机制,为临床治疗COVID-19及研发抗SARS-CoV-2药物提供参考依据。     

SARS-CoV-2受体(ACE2)相关感染致病机制的研究进展

由严重急性综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的2019年新冠病毒(COVID-19)疫情目前仍在全球范围内流行.血管紧张素转换酶2是新冠病毒的受体,介导病毒进入靶细胞.此文对ACE2的相关研究成果进行文献调研,从A...     

新型冠状病毒肺炎临床治疗药物最新研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)正在世界范围内流行.作为冠状病毒,新型冠状病毒(SARS-CoV-2)和严重急性呼吸综合征冠状病毒(SARS-CoV)都通过人血管紧张素转化酶2(ACE2)受体侵入宿主细胞.面对疫情异常严峻的现状,目前尚缺乏疫苗和尚无特异性针对该病毒...     

血管紧张素转换酶2抗新冠病毒药理作用机制的研究进展

血管紧张素转换酶2（ACE2）是肾素-血管紧张素系统负向调节血压的关键因子，主要分布在心脏、肾脏和胃肠等部位。最新研究发现ACE2是新型冠状病毒（SARS-CoV-2）入侵的功能性受体。新型冠状病毒和SARS相关冠状病毒（SARS-CoV）都能利用宿主细胞表面ACE2作为受体，与病毒刺突糖蛋白（Spike）受体结合结构域（RBD）结合发生相互作用，介导病毒入侵宿主细胞。回顾性分析ACE2在抗SARS-CoV中的研究进展，结合目前对新型冠状病毒肺炎（COVID-19）疫情防治的认识及Spike-ACE2蛋白相互作用的最新研究成果，对ACE2抗新型冠状病毒的药理作用机制研究进行简要综述，以期为新冠肺炎抗病毒特效药的研发提供参考。     

血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂在新型冠状病毒肺炎疫情防控中的应用分析

根据《中国心血管病报告》,中国现患心血管病人数约2.9亿,而大量循证医学证据证实了血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)治疗心血管等疾病的价值.ACEI/ARB是肾素-血管紧张素-醛固酮系统(RAAS)的阻滞剂,可上调血管紧张素转换酶2(ACE2)表达水平.而ACE2是新型冠状病毒肺炎(CO...     

感染2019新型冠状病毒的高血压病患者不建议停用血管紧张素转换酶抑制剂及血管紧张素Ⅱ受体阻滞剂

对于感染2019新型冠状病毒(2019-nCoV)的高血压病患者,是否应该停用血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体阻滞剂(ACEI/ARB)类药物,存在两种相反观点。血管紧张素转换酶2(ACE2)已经被证实是肾素-血管紧张素系统(RAS)负向调控的关键酶,激活ACE2/Ang(1-7)/Mas轴后可以拮抗血管紧张素Ⅱ对RAS激活后的有害作用。ACE2也是SARS病毒和2019-nCoV感染细胞的功能性受体,ACE2在2019-nCoV感染中的作用及对新型冠状病毒肺炎病情的影响,目前尚不明确。目前尚没有ACEI/ARB增加2019-nCoV感染风险和加重病情的证据。对感染2019-nCoV的高血压病患者不建议停用ACEI/ARB类药物。     

新型冠状病毒感染疫情中ACEI的争议：下结论还为时尚早

近期,新型冠状病毒感染合并高血压的患者,是否应停用血管紧张素转换酶抑制剂(ACEI)引起了争议。血管紧张素转换酶2(ACE2)是血管紧张素转换酶(ACE)的同源物,两者在血压调控和肺损伤中发挥重要作用。ACE2也是新型冠状病毒感染呼吸道上皮细胞的作用靶点。目前,关于ACEI对新型冠状病毒感染患者的ACE2调控效应出现了不同理论,ACEI/ARB对ACE2的调控效应尚无定论。此外,目前研究结果多数来自于动物实验,尚无临床数据。由于证据有限,因此使用ACEI/ARB类降压药的新型冠状病毒感染患者暂不必换药。     

肾素-血管紧张素系统在COVID-19中作用及药物干预

COVID-19的发病特征为发热、干咳、乏力,严重者可进展为急性呼吸窘迫综合征(ARDS)等,甚至危及生命。SARS-CoV-2可通过血管紧张素转化酶2(ACE2)入侵细胞并导致ACE2表达下调。ACE2表达下调会导致肾素-血管紧张素系统(RAS)的失衡,从而引起后续病理状态发生,RAS在ARDS中也发挥重要的作用。本文总结了RAS系统在COVID-19发病过程中可能存在的作用,以及基于RAS对于COVID-19的治疗可能,为优化治疗及后续研究提供参考。     

沙库巴曲缬沙坦对肾功能保护作用的系统评价和meta分析

目的 系统评价沙库巴曲缬沙坦相比血管紧张转换酶抑制剂(angiotensin-converting enzyme inhibitors,ACEI)或血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)对肾功能的保护作用.方法 检索万方、知网、PubMed、Embase、Clinic...     

The fight against COVID-19: Striking a balance in the renin–angiotensin system

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2), a vital element in the renin–angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. We herein evaluate existing evidence for the molecular alterations within the RAS pathway (e.g., ACE2 and angiotensin II) during SARS-CoV-2 infection and subsequent Coronavirus Disease 2019 (COVID-19). This includes reports regarding potential effect of RAS blockade (e.g., ACE inhibitors and angiotensin II receptor blockers) on ACE2 expression and clinical outcomes in patients with co-morbidities commonly treated with these agents. The collective evidence suggests a dual role for ACE2 in COVID-19, depending on the stage of infection and the coexisting diseases in individual patients. This information is further discussed with respect to potential therapeutic strategies targeting RAS for COVID-19 treatment.     

COVID-19 pandemic: Mechanistic approaches and gender vulnerabilities

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19), a severe respiratory damaging syndrome with serious health complications worldwide. SARS-CoV-2 was unfamilar before the epidemic started in Wuhan, China, in December 2019. COVID-19 is currently a pandemic influencing several countries worldwide. One of the mysteries of the new coronavirus is that it is deadlier for men than women with the male mortality rate is twice as high as that of females.     

合并冠心病与否对新型冠状病毒肺炎患者疾病发展及预后的影响

目的 探讨合并冠心病（CHD）与否对新型冠状病毒肺炎（COVID-19）患者疾病发展及预后的影响。方 法 回顾性分析我院治愈出院的80例COVID-19患者,其中普通型58例、重型14例、危重型8例。按照是否合并 CHD分为2组：合并CHD组36例,未合并CHD组44例。比较2组患者年龄、性别、体质量指数、血氧饱和度、心率、血 压、住院天数、胸部CT明显好转所需天数、临床分型、血管紧张素转换酶抑制剂（ACEI）/血管紧张素Ⅱ受体拮抗剂 （ARB）用药情况等一般资料,以及白细胞计数（WBC）、淋巴细胞计数（LYM）、C反应蛋白（CRP）、肝肾功能等检查结 果的差异。结果 合并CHD组较未合并CHD组患者血氧饱和度降低,心率增快,住院天数、胸部CT好转所需天数延 长,服用ACEI/ARB类药物的患者所占比例升高（均P＜0.05）。合并CHD组较未合并CHD组患者WBC、LYM降低, CRP升高（P＜0.05）。合并CHD组患者重型、危重型所占比例均明显高于未合并CHD组,服用ACEI/ARB类药物的 COVID-19患者重型、危重型所占比例均高于未服用药物患者（P＜0.05）。结论 合并CHD的COVID-19患者病情 更严重。同时,ACEI/ARB类药物的使用有可能加重COVID-19患者的病情。     

Current COVID-19 vaccine candidates: Implications in the Saudi population

AimThe purpose of this review is to discuss the current status of local and international efforts undergoing clinical trials aiming at developing a Coronavirus Disease-2019 (COVID-19) vaccine, and to highlight the anticipated challenges of this vaccine globally and in Saudi Arabia.Present FindingsCOVID-19 vaccine development efforts started in early January 2020 when Chinese scientists shared the Coronavirus genomic sequence in public domain. Approximately 321 research groups initiated the search for a vaccine, out of which 41 have reached phase I/II trails and 11 reached phase-III clinical trials, including approved vaccines for early to limited use. Out of these projects are two labs in the Kingdom of Saudi Arabia still in early stages of development of a COVID-19 vaccine. Several vaccine attempts are being tested from traditional, attenuated virus methods, to new nucleic acid-based designs. However, no vaccine has yet completed clinical trials and reached public domain.In spite of the challenges faced during previous vaccine trials, researchers have found that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 is structurally similar to the (SARS-CoV-1) and the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which caused epidemics in 2003 and 2012 respectively. Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity. The race to develop the vaccine is predominantly for individuals at high risk of developing the infection, i.e. population groups who are most susceptible to experiencing fatal symptoms of the coronavirus. These include patients with comorbidities, above the age of 60 years and people at risk of contracting large viral loads, such as healthcare providers caring for critical admissions in in-patient wards, Intensive Care Units and Emergency Room settings.SummaryMany different vaccine strategies are under development throughout different stages of the research timeline; however, it is estimated that none will show favorable results before end of 2020. For any immunization or interventional prevention/therapy system to reach the public and patients at high risk, it needs to undergo multiple phase trials to ensure safety and effectiveness. In this scoping review we aim to map the literature on COVID-19 vaccines and provide recommendations related to gaps in research, applicability and expected challenges for implementation of nationwide vaccination in Saudi Arabia.     

抗新型冠状病毒肺炎药物靶点的研究进展

自2019年12月以来,新型冠状病毒(SARS-CoV-2)在国内爆发,并且目前已在日本和韩国等地进入高发态势,该病毒导致的新型冠状病毒肺炎(COVID-19)已造成多人感染并有2500余人死亡,世界卫生组织于2020年1月31日宣布疫情为"国际关注的突发公共卫生事件"。抗新型冠状病毒药物是阻止病毒传播以及在宿主体内复制从而引起肺炎的有力武器。综述了抗COVID-19药物靶点以及相应的药物和候选物的研究进展。     

Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight

Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises. There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020). SARS-CoV, MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity. To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.     

我国新型冠状病毒疫苗研发进展及思考

新型冠状病毒(SARS-CoV-2)是继SARS冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)之后又一严重危害人类的病毒。SARS-CoV-2引起的疾病被世界卫生组织命名为COVID-19,具有较高的传染性和病死率。为控制疫情蔓延,我国正应急开展多种技术路线的COVID-19疫苗研发,包括灭活疫苗、重组蛋白疫苗、病毒载体疫苗和核酸疫苗(DNA和mRNA)等,在加快疫苗研发进程的同时把握应急研发进度和科学性之间的平衡,并行解决相关科学问题,在满足安全性的前提下保证疫苗的有效性和质量可控。目前我国研发的腺病毒载体疫苗已率先进入Ⅰ期临床试验,多家企业进入注册检验和滚动提交审评资料阶段。本文对COVID-19疫苗研究进展进行综述,并提出现阶段对此种新疫苗研发的考虑。     

Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking

The effects of obesity and smoking in the coronavirus disease 2019 (COVID-19) pandemic remain controversial. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept. Indeed, obesity, air pollution and smoking associated risk factors share underlying pathophysiologies that are related to the Renin-Angiotensin-System in SARS-CoV-2 infection. The aim of this review is to emphasize the mechanism of receptor-ligand interaction and its impact on the enhanced risk of death due to SARS-CoV-2 infection.     

Crosstalk Between Covid-19 and Associated Neurological Disorders: A Review

COVID-19 is a global pandemic, primarily affecting the pulmonary system but its effects on other systems are not certain. Coronavirus, the causative organism, binds with angiotensin- converting enzyme 2 (ACE2) receptors in the lungs and produces pneumonia-like symptoms. Other than lungs, ACE2 receptors are also seen in the endothelium of blood vessels. Therefore, viruses can bind to the ACE2 that is present in the endothelium of brain blood vessels and thus can invade BBB, leading to neuronal damage. It is also believed that olfactory cells rich in ACE2 receptors may act as the main route of viral spread into various parts of the brain. The reported neurological effects of SARS-CoV-2 include cerebrovascular diseases, ageusia and anosmia, Guillain Barre Syndrome, and viral encephalitis. The extent of neurological involvement in SARS-CoV-2 infection warrants the necessity of further research to systematically classify neurological complications associated with SARS-CoV-2 infection, its diagnosis, and treatment. As ACE2 receptors are present in various other organs, it is obligatory to study the effect of coronavirus on other organs also. Since the long-lasting effects of the COVID-19 are unclear, more studies should be conducted to confirm the effect of the virus on the central nervous system. This review highlights the reported neurological manifestations of SARS-CoV-2 and its mechanism.