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. 2020 Feb 17;9(1):382-385.
doi: 10.1080/22221751.2020.1729069. eCollection 2020.

Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody

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Free PMC article

Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody

Xiaolong Tian et al. Emerg Microbes Infect. .
Free PMC article

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.

Keywords: 2019-nCoV; ACE2; RBD; SARS-CoV; monoclonal antibody.

Figures

Figure 1.
Figure 1.
(a) Phylogenetic analysis of 2019-nCoV spike glycoprotein from its protein BLAST sequences. The neighbour-joining tree was constructed using MEGA X, tested by bootstrap method of 2000 replicates, and edited by the online tool of iTOL (v5). (b) The simulated model of 2019-nCoV RBD binding to SARS-CoV-RBD-specific antibodies (m396, 80R, and F26G19). (c) Protein sequence alignment of 2019-nCoV and SARS-CoV RBD, showing the predominant residues that contribute to interactions with ACE2 or SARS-CoV-specific antibodies. (d) The comparison of the complex structures of SARS-CoV-RBD and SARS-CoV-RBD-specific antibodies (shown in the first row) and models of 2019-nCoV-RBD and SARS-CoV-RBD-specific antibodies (shown in the second row). (e) Binding of monoclonal antibodies to 2019-nCoV RBD determined by ELISA. (f) Binding profiles of 2019-nCoV RBD to ACE2 and antibodies, and (g) competition of CR3022 and ACE2 with 2019-nCoV RBD measured by BLI in OctetRED96. Binding kinetics was evaluated using a 1:1 Langmuir binding model by ForteBio Data Analysis 7.0 software.

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Grant support

This work was supported by grants from the National Natural Science Foundation of China (81822027, 81630090), National Key Research and Development Program of China (2019YFA0904400), National Megaprojects of China for Major Infectious Diseases (2018ZX10301403), Chinese Academy of Medical Sciences (2019PT350002), and the staff from Core Facility of Microbiology and Parasitology, Shanghai Medical College, Fudan University.

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