SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization

Dhiraj Mannar, James W. Saville, Zehua Sun, Xing Zhu, Michelle M. Marti, Shanti S. Srivastava, Alison M. Berezuk, Steven Zhou, Katharine S. Tuttle, Michele D. Sobolewski, Andrew Kim, Benjamin R. Treat, Priscila Mayrelle Silva Castanha, Jana L. Jacobs, Simon M. Barratt-Boyes, John W. Mellors, Dimiter S. Dimitrov, Wei Li and Sriram Subramaniam ()
Additional contact information
Dhiraj Mannar: University of British Columbia
James W. Saville: University of British Columbia
Zehua Sun: University of Pittsburgh School of Medicine
Xing Zhu: University of British Columbia
Michelle M. Marti: University of Pittsburgh
Shanti S. Srivastava: University of British Columbia
Alison M. Berezuk: University of British Columbia
Steven Zhou: University of British Columbia
Katharine S. Tuttle: University of British Columbia
Michele D. Sobolewski: University of Pittsburgh School of Medicine
Andrew Kim: University of Pittsburgh School of Medicine
Benjamin R. Treat: University of Pittsburgh
Priscila Mayrelle Silva Castanha: University of Pittsburgh
Jana L. Jacobs: University of Pittsburgh School of Medicine
Simon M. Barratt-Boyes: University of Pittsburgh
John W. Mellors: University of Pittsburgh School of Medicine
Dimiter S. Dimitrov: University of Pittsburgh School of Medicine
Wei Li: University of Pittsburgh School of Medicine
Sriram Subramaniam: University of British Columbia

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (VH ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32262-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32262-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-32262-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().