Based on the phylogenetic analysis (GISAID accession 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 respiratory 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 coronavirus (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 glycoprotein and mediates the entrance to human respiratory 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 antibodies [9]. Some of the antibodies recognize different epitopes on RBD; e.g. the SARS-CoV neutralizing antibodies 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 antibody m396 as indicated by the complex crystal structure [10] are invariably conserved in 2019-nCoV RBD (Figure 1(d)). In the structure of SARS-CoV-RBD-m396, R395 in RBD formed a salt bridge with D95 of m396-VL. Concordantly, the electrostatic interaction was also observed in the model of 2019-nCoV-RBD-m396, forming by R408 (RBD) and D95 (m396-VL). This analysis suggests that some SARS-CoV-specific monoclonal antibodies may be effective in neutralizing 2019-nCoV. In contrast, the interactions between antibody F26G19 [11] or 80R [12] and the RBD in 2019-nCoV decreased significantly due to the lack of salt bridges formed by R426-D56 in SARS-CoV-RBD-F26G19 or D480-R162 in SARS-CoV-RBD-80R, respectively. Furthermore, while most of the 80R-binding residues on the RBD of SARS-CoV are not conserved on RBD of 2019-nCoV (Figure 1(c)), it is unlikely that the antibody 80R could effectively recognize 2019-nCoV. Therefore, it is urgent to experimentally determine 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.
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.