ArticleNature communications2025
Spike conformational and glycan heterogeneity associated with furin cleavage causes incomplete neutralization of SARS-CoV-2.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- miR-29a and miR-15b Modulate SARS-CoV-2 Beta and Omicron Infection in Human Lung Epithelial Cells.International journal of molecular sciences · 2026Article
- Structural and functional dissection of neutralisation differences among SARS-CoV-2 variants using antigenicity prediction and CR3022 binding analysis.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
SARS-CoV-2 Spike - the sole neutralization target, is highly resilient to the immune pressure driving genetic evolution. While potency and breadth of neutralization are widely studied, the incomplete neutralization - the mechanism of resistance without needing genetic change - remains unexplored. Several monoclonal antibodies, although potent, showed incomplete neutralization of genetically homogeneous pseudovirus suggesting the existence of distinct spike conformations. The residual infectivity at high antibody concentration indicates a viral fraction with intrinsic resistance to the antibody. Although the published studies on spike glycosylation, structure, and conformations provide evidence of spike heterogeneity the precise mechanism for the incomplete neutralization has not been established. In this study, we devise a method to separate the un-neutralized virion population, called as persistent fraction of infectivity (PF), and characterize the viral spike protein. The neutralization resistance of PF is stable and unrelated to the conformational equilibrium that exists in the pseudovirus stock. The spike on the PF is highly cleaved between S1 and S2, adopts the closed conformation, and express more mannosidic glycans on RBD than the total virus population. Our study provides possible explanations for the incomplete neutralization by antibodies and delineates the association between furin cleavage of spike, its conformation and glycosylation.
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