Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus
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DOI：
10.1128/jvi.00127-20
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发表时间：
2020-04-01
影响因子：
5.4
通讯作者：
Li, Fang
中科院分区：
文献类型：
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作者：
Wan, Yushun;Shang, Jian;Li, Fang
近日，一种新型冠状病毒(2019-NCoV)在武汉中国出现，对人类造成类似严重急性呼吸综合征冠状病毒(SARS-CoV)的症状。自2002年SARS-CoV暴发以来，广泛的结构分析揭示了SARS-CoV刺激性蛋白受体结合域(RBD)与其宿主受体血管紧张素转换酶2(ACE2)之间的关键原子水平相互作用，它们调节SARS-CoV的跨物种和人与人之间的传播。在这里，我们基于对SARS-CoV的丰富知识和最新发布的2019-nCoV序列，分析了2019-nCoV的潜在受体用途。首先，2019-nCoV的RBD序列，包括与ACE2直接接触的受体结合基序(RBM)，与SARS-CoV相似，强烈提示2019-nCoV以ACE2为受体。其次，2019-nCoV RBM中的几个关键残基(特别是GIn493)与人ACE2提供了有利的相互作用，这与2019-nCoV对人类细胞感染的能力一致。第三，2019年-nCoV RBM(特别是Asn501)的其他几个关键残基与结合人ACE2的作用相容，但不是理想的，这表明2019-nCoV已经获得了一些人传人的能力。最后，虽然系统发育分析表明蝙蝠起源于2019-nCoV，但2019-nCoV也可能识别来自多种动物物种(小鼠和大鼠除外)的ACE2，这意味着这些动物物种可能是2019-nCoV感染的中间宿主或动物模型。这些分析为深入了解2019-nCoV的受体使用、细胞进入、宿主细胞感染性和动物来源提供了见解，可能有助于对2019-nCoV的疫情监测和预防措施。2019年的今天，nCoV让人想起2002至2003年间的SARS-CoV疫情。我们对SARS-CoV受体识别的长达十年的结构研究已经发现SARS-CoV刺突蛋白与其宿主受体血管紧张素转换酶2(ACE2)之间的关键相互作用，ACE2调节SARS-CoV的跨物种和人与人之间的传播。SARS冠状病毒研究的目标之一是建立一个原子级的病毒-受体相互作用的迭代框架，以促进流行病监测，预测物种特异性受体的使用，并识别潜在的动物宿主和病毒的动物模型。基于2019-nCoV Spike蛋白的序列，我们应用这个预测框架来为2019-nCoV的受体使用和可能的宿主范围提供新的见解。这项研究对这一重复框架进行了强有力的测试，为基础、翻译和公共卫生研究社区提供了预测性见解，可能有助于研究和应对这一新颖的2019-nCoV。
Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly GIn493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-tohuman transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.