Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

Abstract

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 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. Therefore, CR3022 has 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, indicating 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.

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

“…This resemblance is further strengthened by our finding that SARS-CoV S elicited polyclonal Ab responses, potently neutralizing SARS-CoV-2 S-mediated entry into cells. We surmise most of these Abs target the highly conserved S 2 subunit (including the fusion peptide region) based on its structural similarity across SARS-CoV-2 and SARS-CoV, the lack of cross-reactivity of several S B -directed Abs (Tian et al, 2020;Wrapp et al, 2020), and previous reports showing that sera from SARS-CoV-infected individuals target this region (Zhang et al, 2004). We note that most SARS-CoV neutralizing Abs isolated to date target the S B domain and that several of them recognize the RBM and prevent receptor engagement (Hwang et al, 2006;Rockx et al, 2008;Rockx et al, 2010;Traggiai et al, 2004;Walls et al, 2019).…”

COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses

“…This is likely due to the antibody's epitope not overlapping with the divergent ACE2 receptor-binding motif. CR3022 has the potential to be developed as a therapeutic candidate, alone or in combination with other neutralizing antibodies for the prevention and treatment of COVID-19 infection (55).…”

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

“…A 2019-nCoV RBD-SD1 106 fragment (S residues 319-591) was recombinantly expressed, and appropriate folding of this 107 construct was validated by measuring ACE2 binding using biolayer interferometry (BLI) 108 ( Figure 4B). Cross-reactivity of the SARS-CoV RBD-directed mAbs S230, m396 and 80R was 109 then evaluated by BLI (12,(28)(29)(30). Despite the relatively high degree of structural homology 110 between the 2019-nCoV RBD and the SARS-CoV RBD, no binding to the 2019-nCoV RBD 111 could be detected for any of the three mAbs at the concentration tested (1 µM) ( Figure 4C, 112 Supplementary Figure 8).…”