Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic, Engineering and Biotechnology, Tehran, Iran.
Division of Pulmonary, Critical Care, and Sleep Disease, College of Medicine-Jacksonville, University of Florida, Jacksonville, FL, USA.
Mol Biol Rep. 2022 Nov;49(11):10715-10727. doi: 10.1007/s11033-022-07700-x. Epub 2022 Jun 26.
Angiotensin-converting enzyme 2 (ACE2) is known as the major viral entry site for SARS-CoV-2. However, viral tissue tropism and high rate of infectivity do not directly correspond with the level of ACE2 expression in the organs. It may suggest involvement of other receptors or accessory membrane proteins in SARSCoV-2 cell entry.
A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting SARS-CoV-2 cell entry. We used a group of the MeSH terms including "cell entry", "surface receptor", "ACE2", and "SARS-CoV-2". We reviewed all selected papers published in English up to end of February 2022. We found several receptors or auxiliary membrane proteins (including CD147, NRP-1, CD26, AGTR2, Band3, KREMEN1, ASGR1, ANP, TMEM30A, CLEC4G, and LDLRAD3) along with ACE2 that facilitate virus entry and transmission. Expression of Band3 protein on the surface of erythrocytes and evidence of binding with S protein of SARS-CoV-2 may explain asymptomatic hypoxemia during COVID19 infection. The variants of SARS-CoV-2 including the B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.2+ (Delta+), and B.1.1.529 (Omicron) may have different potency to bond with these receptors.
The high rate of infectivity of SARS-CoV-2 may be due to its ability to enter the host cell through a group of cell surface receptors. These receptors are potential targets to develop novel therapeutic agents for SARS-CoV-2.
血管紧张素转换酶 2（ACE2）被认为是 SARS-CoV-2 的主要病毒进入位点。然而，病毒组织嗜性和高感染率与器官中 ACE2 的表达水平并不直接对应。这可能表明其他受体或辅助膜蛋白参与了 SARS-CoV-2 细胞进入。
在 PubMed/Medline、EMBASE 和 Cochrane Library 中进行了系统搜索，以查找报告 SARS-CoV-2 细胞进入的研究。我们使用了一组包括“细胞进入”、“表面受体”、“ACE2”和“SARS-CoV-2”的 MeSH 术语。我们回顾了截至 2022 年 2 月底以英文发表的所有选定论文。我们发现了几种受体或辅助膜蛋白（包括 CD147、NRP-1、CD26、AGTR2、Band3、KREMEN1、ASGR1、ANP、TMEM30A、CLEC4G 和 LDLRAD3）以及 ACE2，它们促进了病毒的进入和传播。红细胞表面 Band3 蛋白的表达以及与 SARS-CoV-2 S 蛋白结合的证据可能解释了 COVID19 感染期间无症状性低氧血症。包括 B.1.1.7（Alpha）、B.1.617.1（Kappa）、B.1.617.2（Delta）、B.1.617.2+（Delta+）和 B.1.1.529（Omicron）在内的 SARS-CoV-2 变体可能与这些受体具有不同的结合能力。
SARS-CoV-2 的高感染率可能是由于其能够通过一组细胞表面受体进入宿主细胞。这些受体是开发 SARS-CoV-2 新型治疗药物的潜在靶点。
