ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic
ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic
复制标题
DOI：
10.1016/j.isci.2020.101384
复制
发表时间：
2020-08-21
期刊：
影响因子：
5.8
通讯作者：
Tabach, Yuval
中科院分区：
文献类型：
--
作者：
Braun, Maya;Sharon, Elad;Tabach, Yuval
2019年12月发生的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）外溢感染引发了前所未有的大流行。与其他冠状病毒一样，SARS-CoV-2通过血管紧张素转换酶2（ACE 2）受体与靶细胞结合。因此，这使得ACE 2研究对于理解冠状病毒的人畜共患病性质和识别新药至关重要。在这里，我们提出了一个系统的分析ACE 2的保护和共进化蛋白网络在1,671真核生物，揭示了一个意想不到的保护模式，在特定的后生动物，植物，真菌和原生生物。我们验证了共同进化的蛋白质网络，并通过使用来自不同来源的数据集成来确定针对该网络的药物列表。我们的计算分析发现了广泛使用的药物，如非甾体抗炎药和血管扩张剂。预计这些药物会干扰ACE 2网络，影响疾病的感染性和病理生理学。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-con-verting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essen-tial for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co -evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We iden-tified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.