AGTR2, One Possible Novel Key Gene for the Entry of SARS-CoV-2 Into Human Cells
AGTR2, One Possible Novel Key Gene for the Entry of SARS-CoV-2 Into Human Cells
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DOI：
10.1109/tcbb.2020.3009099
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发表时间：
2021-07-01
影响因子：
4.5
通讯作者：
Cui, Qinghua
中科院分区：
文献类型：
--
作者：
Cui, Chunmei;Huang, Chuanbo;Cui, Qinghua
最近，已证实ACE2是引起最近全球爆发的严重肺炎的病原体SARS-CoV-2的受体。令人困惑的是，ACE2在多种器官中广泛表达，并且在肺中表达中等但不高，然而肺是主要的感染器官。因此，我们假设可能还有其他一些基因在 SARS-CoV-2 进入人体细胞的过程中发挥着关键作用。在这里，我们发现AGTR2（血管紧张素II受体2型）是一种G蛋白偶联受体，与ACE2有相互作用，并且在肺中高表达，具有高组织特异性。更重要的是，基于 3D 结构的蛋白质-蛋白质相互作用模拟表明，AGTR2 与 SARS-CoV-2 的 Spike 蛋白的结合亲和力高于 ACE2（能量：-8.2 vs. -5.1 [kcal/mol]）。预计许多化合物、生物制剂和中药可以降低 AGTR2 的表达水平。最后，我们认为 AGTR2 可能是 SARS-CoV-2 进入人类细胞的假定新基因，这可以为 SARS-CoV-2 蛋白及其受体的研究提供不同的见解。
Recently, it was confirmed that ACE2 is the receptor of SARS-CoV-2, the pathogen causing the recent outbreak of severe pneumonia around the world. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. Therefore, we hypothesized that there could be some other genes playing key roles in the entry of SARS-CoV-2 into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of SARS-CoV-2 than ACE2 (energy: -8.2 vs. -5.1 [kcal/mol]). A number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted. Finally, we suggest that AGTR2 could be a putative novel gene for the entry of SARS-CoV-2 into human cells, which could provide different insight for the research of SARS-CoV-2 proteins with their receptors.