Conserved role of spike S2 domain N-glycosylation across betacoronaviruses

Qi Yang; Anju Kelkar; Balaji Manicassamy; Sriram Neelamegham

doi:10.1038/s44298-024-00085-7

Back

Conserved role of spike S2 domain N-glycosylation across betacoronaviruses

Journal article

Open access

Peer reviewed

Conserved role of spike S2 domain N-glycosylation across betacoronaviruses

Qi Yang, Anju Kelkar, Balaji Manicassamy and Sriram Neelamegham

Npj viruses, Vol.3(1), 4

01/25/2025

DOI: 10.1038/s44298-024-00085-7

PMCID: PMC11762317

PMID: 40295734

Files and links (1)

url

https://doi.org/10.1038/s44298-024-00085-7View

Published (Version of record) Open Access

Abstract

Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five ‘stem N-glycans’ located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human betacoronaviruses.

Epidemiology

Public Health

Virology

631/326/596

631/45

Biomedical and Life Sciences

Biomedicine

Vaccine

Details

Title: Subtitle: Conserved role of spike S2 domain N-glycosylation across betacoronaviruses
Creators: Qi Yang - University at Buffalo, State University of New York
Anju Kelkar - University at Buffalo, State University of New York
Balaji Manicassamy - University of Iowa
Sriram Neelamegham - University at Buffalo, State University of New York
Resource Type: Journal article
Publication Details: Npj viruses, Vol.3(1), 4
DOI: 10.1038/s44298-024-00085-7
PMID: 40295734
PMCID: PMC11762317
eISSN: 2948-1767
Publisher: Nature Publishing Group UK
Grant note: AI174584; UL1TR001412 / National Institutes of Health (http://dx.doi.org/10.13039/100000002)
Language: English
Date published: 01/25/2025
Academic Unit: Microbiology and Immunology
Record Identifier: 9984775264102771

Metrics

6 Record Views

See more details