/10.1080/221751.2020.1729069 ®EMi©tbr&n LETTER OPEN ACCESS Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus- specific human monoclonal antibody f Basic Medical y of S torRort%oCa Zhongshan Hospital,Fudan University,Shanghai,Peoples Republic of China avins (2019-nCov ea sing the re ntly,h h 2019-nC0 for rapid dev nes and theraper 019 against 201 RBD (KD f 63 nM).T cs,alone or in combination h other the pre n and t女eatu 20 RBD of SARS. prot CoV and 2019- ne still necessary to develop novel monoclonal anti ARTICLE HISTORY Received 27 January 2020;Revised 2 February 2020:Accepted 3 February 2020 KEYWORDS 2019-nCoV:SARS-CoV:ACE2:monoclonal antibody:RBD coronairnuswhidh ngiotensin converting nzyme 2 (ACE? oratory-confirmed human infections in China,includ- 8].More specifically,the 193 amino acid length ing 259 deaths,and 132 exported cases in 23 countries (N318-V510)receptor binding domain(RBD)withir outside of China (https://www.who.int/emergencies/ the S protein is the critical target for neutralizing anti I-coronavirus-2 019/situation-reports) odies 9 e of t recognize diff efective antiviral neutralizing ant Rased on the nhylog etic analysis (GISaid acce to the SARS-CoV RBD and neutralized the virus in a sion no.EPI_ISL_402124)[2),2019-nCoV belongs to synergistic fashion [5].We predicted the conformation lineage B betacoronavirus and shares high sequence of 2019-nCoV RBD as well as its complex structures identity with that of bat or human severe acute respir ithseveral eutralizing antibodies,and found that mo ults support the inte ant us s of RBD in 201 virus (SARS-Cov)have been identified [3-7).These (Figure 1(c)).For instance.residues in RBD of SARS- antibodies target the spike protein (S)of SARS-CoV Cov that make polar interactions with a neutralizing ing.131 enlingfudan.edu.cn M E 6 G Su sed at https:// g/10.1080/22221751.2020.1779069LETTER Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus￾specific human monoclonal antibody Xiaolong Tiana#, Cheng Lia#, Ailing Huanga , Shuai Xiaa , Sicong Lua , Zhengli Shi b , Lu Lua , Shibo Jiang a , Zhenlin Yangc , Yanling Wua and Tianlei Ying a a MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; b CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of China; c Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China ABSTRACT 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. ARTICLE HISTORY Received 27 January 2020; Revised 2 February 2020; Accepted 3 February 2020 KEYWORDS 2019-nCoV; SARS-CoV; ACE2; monoclonal antibody; RBD Very recently, a novel coronavirus which was tempor￾arily named “2019 novel coronavirus (2019-nCoV)” emerged in Wuhan, China [1]. As of 1 February 2020, 2019-nCoV has resulted in a total of 11,821 lab￾oratory-confirmed human infections in China, includ￾ing 259 deaths, and 132 exported cases in 23 countries outside of China (https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/situation-reports). Currently, there is no vaccine or effective antiviral treatment against 2019-nCoV infection. Based on the phylogenetic analysis (GISAID acces￾sion no. EPI_ISL_402124) [2], 2019-nCoV belongs to lineage B betacoronavirus and shares high sequence identity with that of bat or human severe acute respir￾atory syndrome coronavirus-related coronavirus (SARSr-CoV) and bat SARS-like coronavirus (SL￾CoV) (Figure 1(a)). In previous studies, a number of potent monoclonal antibodies against SARS corona￾virus (SARS-CoV) have been identified [3–7]. These antibodies target the spike protein (S) of SARS-CoV and SL-CoVs, which is a type I transmembrane glyco￾protein and mediates the entrance to human respirat￾ory epithelial cells by interacting with cell surface receptor angiotensin-converting enzyme 2 (ACE2) [8]. More specifically, the 193 amino acid length (N318-V510) receptor binding domain (RBD) within the S protein is the critical target for neutralizing anti￾bodies [9]. Some of the antibodies recognize different epitopes on RBD; e.g. the SARS-CoV neutralizing anti￾bodies CR3014 and CR3022 bound noncompetitively to the SARS-CoV RBD and neutralized the virus in a synergistic fashion [5]. We predicted the conformation of 2019-nCoV RBD as well as its complex structures with several neutralizing antibodies, and found that the modelling results support the interactions between 2019-nCoV RBD and certain SARS-CoV antibodies (Figure 1(b)). This could be due to the relatively high identity (73%) of RBD in 2019-nCoV and SARS-CoV (Figure 1(c)). For instance, residues in RBD of SARS￾CoV that make polar interactions with a neutralizing © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. CONTACT Tianlei Ying tlying@fudan.edu.cn Room 504, Fosun Building, 131 Dong-an Road, Shanghai 200032, People’s Republic of China; Yanling Wu yanlingwu@fudan.edu.cn Room 504, Fosun Building, 131 Dong-an Road, Shanghai 200032, People’s Republic of China; Zhenlin Yang yang_zhenlin@fudan.edu.cn Room 504, Fosun Building, 131 Dong-an Road, Shanghai 200032, People’s Republic of China # These authors contributed equally to this article. Supplemental data for this article can be accessed at https://doi.org/10.1080/22221751.2020.1729069. Emerging Microbes & Infections 2020, VOL. 9 https://doi.org/10.1080/22221751.2020.1729069