Talotta Rossella, Roberston Erle S
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Messina, University Hospital "G. Martino" Messina, Italy.
Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania Philadelphia, USA.
Am J Clin Exp Immunol. 2020 Dec 15;9(5):73-80. eCollection 2020.
ACE2 is crucially involved in the infection sustained by SARS-CoV-2, as it allows the entry of the virus into target cells while counteracting local inflammation, oxidative stress, and fibrosis. In this narrative review, we aim to discuss the usefulness of ACE2-derived peptides in the infection sustained by SARS-CoV-2.
A total of 49 papers pertinent to the purpose of the review were selected from the PubMed and Google Scholar databases. Clinical trials registered at ClinicalTrials.gov and dealing with the use of ACE2-derived medications in COVID-19 were also searched and discussed.
Preclinical and clinical evidence shows that drugs mimicking or potentiating the effects of ACE2 may reduce the viral load and dampen the inflammatory and fibrotic pathways leading to respiratory distress. ACE2-derived therapeutic peptides may have a better pharmacokinetic and pharmacodynamic profile than other ACE2-based medications. They could be easily screened through peptide libraries and chemically modified in order to ameliorate the pharmacological properties. Furthermore, their local administration an intranasal delivery or inhalation may reduce the risk of systemic side effects, thus conferring a good safety profile.
ACE2-derived peptides may play a dual beneficial role in COVID-19, by either preventing virus spread or inhibiting the secretion of pro-inflammatory mediators in airways. Viral, host, and environmental factors may affect the effectiveness of this therapeutic approach to a various extent and represent therefore a matter of investigation for future studies.
血管紧张素转换酶2（ACE2）在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发的感染中起关键作用，因为它能使病毒进入靶细胞，同时对抗局部炎症、氧化应激和纤维化。在这篇叙述性综述中，我们旨在探讨ACE2衍生肽在SARS-CoV-2引发的感染中的作用。
从PubMed和谷歌学术数据库中总共筛选出49篇与本综述目的相关的论文。还检索并讨论了在ClinicalTrials.gov上注册的、涉及在2019冠状病毒病（COVID-19）中使用ACE2衍生药物的临床试验。
临床前和临床证据表明，模拟或增强ACE2作用的药物可能会降低病毒载量，并抑制导致呼吸窘迫的炎症和纤维化途径。ACE2衍生的治疗性肽可能比其他基于ACE2的药物具有更好的药代动力学和药效学特征。它们可以通过肽库轻松筛选，并进行化学修饰以改善药理特性。此外，它们的局部给药（鼻内给药或吸入）可能会降低全身副作用的风险，因此具有良好的安全性。
ACE2衍生肽可能在COVID-19中发挥双重有益作用，要么阻止病毒传播，要么抑制气道中促炎介质的分泌。病毒、宿主和环境因素可能在不同程度上影响这种治疗方法的有效性，因此是未来研究的一个调查重点。
