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

By Xiao-long Tian, Cheng Li, Ailing Huang, Shuai Xia, Sicong Lu, Zhènglì Shí, Lu Lu, Shibo Jiang, Zhenlin Yang, Yanling Wu and 1 more. bioRxiv, 2020

1,225 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/c8debc2e2702b4273fb921baea7c07a34fbf6cf9

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In Infectious Diseases

1. D. Veesler
2. F. Krammer
3. A. Walls
4. M. A. Tortorici
5. L. Du
6. C. Hillyer
7. Ian A. Wilson
8. Andrew T. McGuire

Citations in the corpus

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response (2020, neutral): “This virus was first identified in the respiratory tract of patients with pneumonia in Wuhan, Hubei China, in December 2019 which was then indicated as a newly identified β-coronavirus (nCoV) [3, 4] .”
• Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays (2020, methodology): “Spike expression was measured by staining with in-house produced CR3022 antibody [43–45] at a concentration of 10 μg/mL followed by staining with an anti-human Fc antibody conjugated to APC (Jackson Labs, 109135-098) at a 1:100 dilution.”
• A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV (2020, background): “can bind to the RBD of SARS-CoV-2 (5).”
• Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses (2020, background): “Notably, a SARS-CoV RBD-specific human neutralizing mAb, CR3022, could bind SARSCoV-2 RBD with high affinity and recognize an epitope on the RBD that does not overlap with the ACE2-binding site [13].”
• SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract (2020, neutral): “In line with previous reports (Tian et al., 2020; Wrapp et al., 2020), our data show that several SARS-CoV RBD-binding nAbs fail to neutralize SARS-CoV-2, suggesting distant antigenicity within the RBD domains between the two viruses.”
• COVID-19 neutralizing antibodies predict disease severity and survival (2020, neutral): “Quantitation for both assays was achieved using a standard curve consisting of purified IgG, IgM, and IgA isotype of a monoclonal antibody, CR3022 (Figure 2A), that cross-reacts to bind both SARS-CoV and SARS-CoV-2 RBD (Figure S2B) (ter Meulen et al., 2006; Tian et al., 2020).”
• Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells (2020, neutral): “Indeed, several studies have suggested that SARS-CoV-neutralizingmAbs could cross-neutralize SARSCoV-2 (Wang et al., 2020; Tian et al., 2020; Lv et al., 2020), which further highlights the resemblance between the RBDs of SARSCoV and SARS-CoV-2.”
• Coronavirus disease 2019 (COVID-19): current status and future perspectives (2020, background): “In order to engage a host receptor, the receptor-binding domain (RBD) of the S1 subunit undergoes hinge-like conformational movements, which transiently hide or expose the determinants of receptor binding [19 , 20] .”