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August 5, 2026PLoS PathogensOpen Access

Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit

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Authors

LZLing ZhouHenan Cancer HospitalCHChing‐Lin HsiehNational Taiwan University HospitalSLSarah R. LeistUniversity of North Carolina at Chapel Hill

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Implication

Randomized trial explores the structural dynamics of a cryptic epitope on SARS-CoV-2, highlighting its implications.

Key Points

  • The study aims to characterize a conserved cryptic epitope on the S2 subunit of SARS-CoV-2 and examine antibodies targeting it.
  • Isolated S2-targeted antibodies from COVID-19 convalescent donors using yeast surface display.
  • Conducted biophysical characterization of these antibodies against varying spike conformations.
  • Used cryo-electron microscopy to define structural features of the cryptic epitope.
  • Antibodies preferentially bound to open spike conformations and a stabilized S2 construct.
  • Weak neutralization activity observed against SARS-CoV-2 pseudoviruses; failed to neutralize authentic viruses.
  • No protective effect in a lethal mouse challenge model using a mouse-adapted SARS-CoV-2 strain.

Cite This Study

Zhou et al. (2026) studied this question.

synapsesocial.com/papers/6a72e823226790f370657a7ahttps://doi.org/10.1371/journal.ppat.1014391
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