USL Umbria 1, Pharmaceutical Department, Perugia, Italy.
USL Umbria 2, Pharmaceutical Department, Terni, Italy.
Drug Discov Today. 2021 Apr;26(4):870-874. doi: 10.1016/j.drudis.2021.01.010. Epub 2021 Jan 21.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global Coronavirus 2019 (COVID-19) pandemic, resulting in thousands of deaths worldwide and representing a health challenge with few precedents in human history. Angiotensin-converting enzyme 2 (ACE-2) facilitates the access of SARS-CoV-2 to cells. Therapeutic agents acting on the renin-angiotensin system (RAS) might be able to modulate the concentration of ACE-2 and the various components of the system. Here, we discuss current pharmacological, molecular, and clinical evidence to investigate whether drugs acting on RAS with modulation of the ACE-2 concentration have added value in combating SARS-CoV-2 infection. We also highlight the possible deleterious action of the ACE/Ang-II/AT-1r axis and possible beneficial role of the ACE-2/Ang 1-7/MasR axis in acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2, discussing the possibility of addressing the various RAS components with drug treatments to improve clinical outcomes.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是导致当前全球 2019 年冠状病毒病(COVID-19)大流行的罪魁祸首,导致全球数千人死亡,这是人类历史上前所未有的健康挑战。血管紧张素转换酶 2(ACE-2)促进了 SARS-CoV-2 进入细胞。作用于肾素-血管紧张素系统(RAS)的治疗药物可能能够调节 ACE-2 的浓度和系统的各种成分。在这里,我们讨论了当前的药理学、分子和临床证据,以研究作用于 RAS 并调节 ACE-2 浓度的药物在对抗 SARS-CoV-2 感染方面是否具有附加价值。我们还强调了 ACE/Ang-II/AT-1r 轴的可能有害作用,以及 ACE-2/Ang 1-7/MasR 轴在 SARS-CoV-2 引起的急性呼吸窘迫综合征(ARDS)中的可能有益作用,讨论了用药物治疗来解决各种 RAS 成分以改善临床结果的可能性。