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宿主细胞蛋白如 ACE2、ADAM17、TMPRSS2 和雄激素受体是否可以成为 SARS-CoV-2 感染的有效靶点?

Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2 Infection?

机构信息

Department of Biochemistry, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra-282004, India.

Department of Immunology, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra-282004, India.

出版信息

Curr Drug Targets. 2021;22(10):1149-1157. doi: 10.2174/1389450121999201125201112.

Abstract

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- -2), which caused a large disease outbreak in Wuhan, China in December 2019, is currently spreading across the world. Along with binding of the virus spike with the host cell receptor, fusion of the viral envelope with host cell membranes is a critical step in establishing successful infection of SARS-CoV-2. In this entry process, a diversity of host cell proteases and androgen receptor play a very important role directly or indirectly. These features of SARS-CoV-2 entry contribute to its rapid spread and severe symptoms, high fatality rates among infected patients. This review is based on the latest published literature including review articles, research articles, hypothetical manuscript, preprint articles and official documents. The literature search was made from various published papers on physiological aspects relevant to SARS-CoV and SARS-CoV-2. In this report, we focus on the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection. The hypotheses put forth by us are based on the role played by the proteases ACE2, ADAM17, TMPRSS2 and AR in SARS-CoV-2 infection, which were deduced based on various studies. We have also summarized how these host proteins increase the pathology and the infective ability of SARS-CoV-2 and we posit that their inhibition may be a therapeutic option for preventing SARS-CoV-2 infection.

摘要

一种新型的β冠状病毒,即严重急性呼吸综合征冠状病毒 2(SARS-CoV-2),于 2019 年 12 月在中国武汉引发了大规模疾病爆发,目前正在全球范围内传播。除了病毒刺突与宿主细胞受体的结合外,病毒包膜与宿主细胞膜的融合是 SARS-CoV-2 成功感染的关键步骤。在这个进入过程中,多种宿主细胞蛋白酶和雄激素受体直接或间接地发挥了非常重要的作用。SARS-CoV-2 进入的这些特征导致了其快速传播和严重症状,感染患者的高死亡率。本综述基于最新发表的文献,包括综述文章、研究文章、假设手稿、预印本文章和官方文件。文献检索是从与 SARS-CoV 和 SARS-CoV-2 相关的生理学方面的各种已发表论文中进行的。在本报告中,我们重点介绍宿主细胞蛋白酶(ACE2、ADAM17、TMPRSS2)和雄激素受体(AR)在 SARS-CoV-2 感染中的作用。我们提出的假设是基于蛋白酶 ACE2、ADAM17、TMPRSS2 和 AR 在 SARS-CoV-2 感染中所起的作用,这些作用是根据各种研究推断出来的。我们还总结了这些宿主蛋白如何增加 SARS-CoV-2 的病理学和感染能力,并认为抑制它们可能是预防 SARS-CoV-2 感染的一种治疗选择。

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