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SARS-CoV-2 刺突糖蛋白作为药物和疫苗靶点:与 ACE2 和抗体复合物的结构见解。

The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies.

机构信息

Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.

出版信息

Cells. 2020 Oct 22;9(11):2343. doi: 10.3390/cells9112343.

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease (COVID-19) pandemic, has so far resulted in more than 1.1 M deaths and 40 M cases worldwide with no confirmed remedy yet available. Since the first outbreak in Wuhan, China in December 2019, researchers across the globe have been in a race to develop therapies and vaccines against the disease. SARS-CoV-2, similar to other previously identified family members, encodes several structural proteins, such as spike, envelope, membrane, and nucleocapsid, that are responsible for host penetration, binding, recycling, and pathogenesis. Structural biology has been a key player in understanding the viral infection mechanism and in developing intervention strategies against the new coronavirus. The spike glycoprotein has drawn considerable attention as a means to block viral entry owing to its interactions with the human angiotensin-converting enzyme 2 (ACE2), which acts as a receptor. Here, we review the current knowledge of SARS-CoV-2 and its interactions with ACE2 and antibodies. Structural information of SARS-CoV-2 spike glycoprotein and its complexes with ACE2 and antibodies can provide key input for the development of therapies and vaccines against the new coronavirus.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是导致冠状病毒病(COVID-19)大流行的病原体,迄今为止,它已在全球造成超过 110 万人死亡和 4000 多万人感染,目前尚无有效的治疗方法。自 2019 年 12 月中国武汉首次爆发疫情以来,全球研究人员一直在竞相开发针对该疾病的治疗方法和疫苗。SARS-CoV-2 与其他先前确定的家族成员类似,编码几种结构蛋白,如刺突、包膜、膜和核衣壳,这些蛋白负责宿主穿透、结合、回收和发病机制。结构生物学一直是理解病毒感染机制和开发针对新型冠状病毒干预策略的关键因素。刺突糖蛋白因其与作为受体的人血管紧张素转换酶 2(ACE2)的相互作用而引起了相当大的关注,因为它是一种阻断病毒进入的手段。在这里,我们回顾了 SARS-CoV-2 的最新知识及其与 ACE2 和抗体的相互作用。SARS-CoV-2 刺突糖蛋白及其与 ACE2 和抗体的复合物的结构信息可为针对新型冠状病毒的治疗方法和疫苗的开发提供关键信息。

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