The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Open accessAbstract
There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
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Cites
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Metadata
- Authors
- Huo, J., Zhao, Y., Ren, J., Zhou, D., Duyvesteyn, H. M. E., Ginn, H. M., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., Tan, T. K., Rijal, P., Coombes, N., Bewley, K. R., Tree, J. A., Radecke, J., Paterson, N. G., Supasa, P., Mongkolsapaya, J., Screaton, G. R., Carroll, M., Townsend, A., Fry, E. E., Owens, R. J., & Stuart, D. I.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 28
- Issue
- 3
- Pages
- 445-454.e6
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W3035950190
- Cited by
- 332
- References
- 9
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Huo, J., Zhao, Y., Ren, J., Zhou, D., Duyvesteyn, H. M. E., Ginn, H. M., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., Tan, T. K., Rijal, P., Coombes, N., Bewley, K. R., Tree, J. A., Radecke, J., Paterson, N. G., Supasa, P., Mongkolsapaya, J., . . . Stuart, D. I. (2020). Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2020.06.010
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