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Spike Antibody-mediated Neutralization of SARS-CoV-2

30-Jun-2020

 

As the COVID-19 pandemic rages largely unabated, researchers are working intensely to identify vulnerable targets of the SARS-CoV-2 virion for therapeutics and vaccine development. Major focus is on the virus’s spike protein, which mediates viral binding and membrane fusion through interaction with the host cell’s ACE2 receptor. In their new study in Cell Host & Microbe, Huo et al. performed crystallographic analysis in conjunction with neutralization and cryo-EM studies to dissect the interaction between the SARS-CoV-2 spike receptor binding domain (RBD), ACE2, and the RBD-binding monoclonal antibody CR3022 (1). Obtained originally from a convalescent SARS-CoV patient and distinguished by its cross-reactivity with SARS-CoV-2, CR3022 is known to recognize an epitope in these RBDs that is different than the ACE2 binding site. Nevertheless, the authors showed evidence for an allosteric effect of CR3022 on ACE2 binding to the RBD. Their structural modeling and cryo-EM studies revealed that CR3022 binds to a highly conserved site in the RBD, leading to destabilization of the prefusion spike conformation. This premature transition of spike to a post-fusion context offers a novel mechanism for coronaviral inactivation that is distinct from interference of receptor association. In addition, the authors’ findings regarding the importance of the RBD sequence constituting the CR3022 epitope for prefusion spike stabilization explains the lack of described escape mutants. All told, this study by Huo et al. presents intriguing possibilities for the potential use of CR3022, either alone or in combination with a receptor-blocking antibody, as a COVID-19 therapeutic and as a guide for vaccine strategies.

See All Reagents for COVID-19 Research

 

Highlighted Products

Recombinant Citation-Support Protein Overexpression 

SARS-CoV / SARS-CoV-2 (COVID-19) Spike antibody [CR3022] (GTX01555)

SARS-CoV / SARS-CoV-2 (COVID-19) Spike antibody [CR3022] (GTX01555)

SARS-CoV-2 (COVID-19) Spike S1 antibody [HL6] (GTX635654)

SARS-CoV-2 (COVID-19) Spike S1 antibody [HL6] (GTX635654)

SARS-CoV-2 (COVID-19) Nucleocapsid antibody [HL344] (GTX635679)

SARS-CoV-2 (COVID-19) Nucleocapsid antibody [HL344] (GTX635679)

SARS-CoV / SARS-CoV-2 (COVID-19) Spike antibody [1A9] (GTX632604)

SARS-CoV / SARS-CoV-2 (COVID-19) Spike antibody [1A9] (GTX632604)

 

Reference:

1.Cell Host Microbe. 2020 Jun 19;S1931-3128(20)30351-6.