Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody.
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody.
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DOI：
10.1080/22221751.2020.1729069
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发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Ying, T. L.
中科院分区：
文献类型：
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作者：
Tian, Xiao-long;Li, Cheng;Ying, T. L.
新发现的2019年新型冠状病毒(2019-nCoV)已导致11900多例经实验室确认的人类感染，包括259例死亡，对人类健康构成严重威胁。然而，目前还没有特效的抗病毒治疗或疫苗。考虑到2019-nCoV和SARS-CoV受体结合域(RBD)的同源性较高，迫切需要评估抗SARS CoV抗体与2019-nCoV刺突蛋白的交叉反应性，这可能对快速开发针对2019-nCoV的疫苗和治疗性抗体具有重要意义。在这里，我们首次报道了SARS冠状病毒特异性的人单抗CR3022可以与2019-nCoV RBD(Kd6.3 NM)结合。在2019-nCoV RBD范围内，CR3022的表位与ACE2结合位点不重叠。这些结果表明，CR3022可能有潜力单独或与其他中和抗体联合开发用于预防和治疗2019-nCoV感染的候选治疗药物。有趣的是，一些针对SARS-CoV ACE2结合位点的最有效的SARS-CoV特异性中和抗体(如M396、CR3014)未能结合2019-nCoV刺突蛋白，这意味着SARS-CoV与2019-nCoV RBD的RBD差异对中和抗体的交叉反应具有关键影响，仍有必要开发能够与2019-nCoV RBD特异结合的新型单抗。
The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.