Renin-angiotensin system at the heart of COVID-19 pandemic
Renin-angiotensin system at the heart of COVID-19 pandemic
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DOI：
10.1016/j.biochi.2020.04.008
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发表时间：
2020-07-01
期刊：
影响因子：
3.9
通讯作者：
Iannelli, Antonio
中科院分区：
文献类型：
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作者：
Alifano, Marco;Alifano, Pietro;Iannelli, Antonio
COVID-19大流行的重要方面仍然模糊不清。血管紧张素转换酶2 （Angiotensin converting enzyme, ACE2）是肾素-血管紧张素系统的一个组成部分，主要在肺泡上皮细胞上表达，是SARS-CoV-2的人类细胞受体，SARS-CoV-2是COVID- 19的病原体。我们强烈鼓励这样一个概念，即彻底考虑受体-配体相互作用应保持在感染科学辩论的核心。在这个想法中，整个肾素-血管紧张素系统必须被评估。我们假设，从流行病学和临床的角度来看，与种族、环境、行为、相关疾病和涉及这一复杂系统的药物有关的因素可能是导致异常情况的原因，但是，综合起来，这些因素可以解释当前疫情的大多数方面。我们决定用戏剧来类比，并推测在这场悲剧中可能产生的影响：1)空气污染通过二氧化氮对ACE2表达的干扰；2)尼古丁的双重作用；3) ACE2多态性的假设参与，其与种族因素和心血管疾病易感性的关系似乎很有趣；4)对高血压感染严重程度的影响以及肾素/血管紧张素系统相关药物的作用，最后，5)氯喹可能的帮助作用，由于它能够通过改变糖基化来改变ACE2对病毒刺突蛋白的亲和力。这篇假设论文迫切呼吁制定研究计划，旨在质疑这场悲剧的假定主角是否是COVID-19的现实演员。(C) 2020 Elsevier B.V.和Societe Francaise de Biochimie et Biologie molecular （SFBBM）。版权所有。
Significant aspects of COVID-19 pandemic remain obscure. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID- 19. We strongly encourage the concept that thorough considerations of receptor-ligand interactions should be kept at the heart of scientific debate on infection. In this idea, the whole renin-angiotensin system has to be evaluated. We hypothesize that factors related to ethnicity, environment, behaviors, associated illness, and medications involving this complex system are probably responsible for situations regarded as anomalous from both an epidemiological and a clinical point of view, but, taken together, such factors may explain most of the aspects of current outbreak. We decided to use the analogy of a play and speculate about the possible impact in this tragedy of 1) air pollution via the interference of nitrogen dioxide on ACE2 expression; 2) the dual role of nicotine; 3) the hypothetical involvement of ACE2 polymorphisms, the relationships of which with ethnic factors and susceptibility to cardiovascular disease seems intriguing; 4) the impact on the severity of infection of hypertension and related medications acting on the renin/angiotensin system, and, finally, 5) the possible helpful role of chloroquine, thanks to its capacity of modifying ACE2 affinity to the viral spike protein by altering glycosylation. This hypothesis paper is an urgent call for the development of research programs that aim at questioning whether the putative protagonists of this tragedy are real-life actors in COVID-19. (C) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.