Does the SARS-CoV-2 spike really have an Achilles heel?
Shiv Pillai
Shiv Pillai
Published April 17, 2023
Citation Information: J Clin Invest. 2023;133(8):e168080. https://doi.org/10.1172/JCI168080.
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Commentary

Does the SARS-CoV-2 spike really have an Achilles heel?

Abstract

The continued emergence of SARS-CoV-2 variants and waning vaccine immunity are some of the factors that drive the continuing search for more effective treatment and prevention options for COVID-19. In this issue of the JCI, Changrob, et al. describe an anti-SARS-CoV-2 spike antibody, isolated from a patient, that targets a vulnerable site on the spike protein receptor binding domain when it adopts a configuration called the “up” conformation. This antibody cross-neutralized all variants studied, including recent Omicron subvariants, and was protective against multiple variants in a hamster model. These results are of interest when considering the next generation of prophylactic and therapeutic antibodies for COVID-19, but they may also shape future approaches to vaccination against SARS-CoV-2.

Authors

Shiv Pillai

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Figure 1

The broadly neutralizing S728-1157 antibody can neutralize all known SARS-CoV-2 variants and subvariants.

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The broadly neutralizing S728-1157 antibody can neutralize all known SAR...
The S728-1157 antibody binds to a site of the Spike RBD when it is in the up conformation. When the Spike RBD is in the up conformation, the RBS is able to make contact with ACE2 on host cells to mediate viral entry. The S728-1157 antibody requires the invariant CDR-H1 and CDR-H2 loops, encoded by IGHV3-66, for binding. It also extensively utilizes the unique CDR-H3 loop in an unmutated form.