Kumar, Sahil and Delipan, Rathina and Sharma, Chanchal and Jadoun, Jyoti and Kanjo, Kawkab and Singh, Randhir and Rajmani, Raju and Deshpande, Suprit and Pandey, Rajesh and Thakur, Krishan G and Bhattacharya, Jayanta and Sanders, Rogier W and van Gils, Marit J and Varadarajan, Raghavan and Ringe, Rajesh P (2025) Spike conformational and glycan heterogeneity associated with furin cleavage causes incomplete neutralization of SARS-CoV-2. Nat. Commun., 16 (1). p. 10130.
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 01 Feb 2026 14:12 |
| Last Modified: | 01 Feb 2026 14:12 |
| URI: | http://crdd.osdd.net/open/id/eprint/3239 |
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