Ahsan Tamim, Sajib Abu Ashfaqur
Department of Genetic Engineering & Biotechnology, Bangabandhu Sheikh Mujibur Rahman Maritime University, Dhaka, 1216, Bangladesh.
Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, 1000, Bangladesh.
Biochem Biophys Rep. 2021 Jul;26:100982. doi: 10.1016/j.bbrep.2021.100982. Epub 2021 Mar 29.
Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1 and potentially interfere with the entry of SARS-CoV-2 inside the host cells.
呼吸道传播是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的主要途径。血管紧张素I转换酶2（ACE2）是已知的SARS-CoV-2表面刺突糖蛋白进入人类细胞的受体。最近一项研究报告称，在多种人类肺上皮细胞样本中，ACE2表达缺失或水平较低。三个生物项目（PRJEB4337、PRJNA270632和PRJNA280600）均发现，与ACE2的极低表达相比，人类肺部中ACE1（ACE2的同源物，也称为ACE）表达丰富。事实上，与ACE2相比，ACE1具有更广泛、更丰富的组织分布。尽管从ACE1和ACE2的一级序列比对中并不明显，但X射线晶体结构比较显示，这些蛋白质的肽酶结构域（PD）区域存在显著相似性，已知（对于ACE2而言）该区域与SARS-CoV-2刺突蛋白的受体结合结构域（RBD）相互作用。介导与病毒刺突蛋白相互作用的ACE2中的关键氨基酸在ACE1的PD中也存在且排列顺序相同。分析预测SARS-CoV-2刺突蛋白与ACE1和ACE2具有类似的相互作用。此外，本研究从1263种已获批药物的列表中预测，这些药物可能与ACE2和/或ACE1相互作用，并可能干扰SARS-CoV-2进入宿主细胞。
