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.

中文翻译：

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AGTR2，一种可能使 SARS-CoV-2 进入人体细胞的新型关键基因

近日，经证实 ACE2 是 SARS-CoV-2 的受体，SARS-CoV-2 是导致近期全球爆发严重肺炎的病原体。令人困惑的是ACE2 在多种器官中广泛表达，在肺中中等但不高度表达，但肺是主要受感染的器官。因此，我们假设可能还有其他一些基因在 SARS-CoV-2 进入人体细胞中发挥关键作用。在这里我们发现AGTR2（血管紧张素 II 受体 2 型），一种 G 蛋白偶联受体，与 ACE2 在肺中高度表达，具有高组织特异性。更重要的是，基于 3D 结构的蛋白质-蛋白质相互作用的模拟表明，与 SARS-CoV-2 的 Spike 蛋白相比，AGTR2 显示出更高的结合亲和力 ACE2（能量：-8.2 vs. -5.1 [kcal/mol]）。一些可以降低基因表达水平的化合物、生物制剂和中药AGTR2 被预测。最后，我们建议AGTR2 可能是 SARS-CoV-2 进入人体细胞的推定新基因，可为 SARS-CoV-2 蛋白及其受体的研究提供不同的见解。