Immune Antibodies Recognizing the Stem Region of SARS-CoV-2 Spike Protein: Molecular Modelling and In Vitro Study of Synthetic Peptides Presentation to the Antibodies

Aliper, E. T.; Ryzhov, I. M.; Obukhova, P. S.; Tuzikov, A. B.; Galanina, O. E.; Ziganshina, M. M.; Sukhikh, G. T.; Krylov, N. A.; Henry, S. M.; Efremov, R. G.; Bovin, N. V.

doi:10.1101/2025.03.20.644166

bioRxiv · 10.1101/2025.03.20.644166

Immune Antibodies Recognizing the Stem Region of SARS-CoV-2 Spike Protein: Molecular Modelling and In Vitro Study of Synthetic Peptides Presentation to the Antibodies

Aliper, E. T.·Ryzhov, I. M.·Obukhova, P. S.·Tuzikov, A. B.·Galanina, O. E.·Ziganshina, M. M.·Sukhikh, G. T.·Krylov, N. A.·Henry, S. M.·Efremov, R. G.·Bovin, N. V.

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Abstract

Antibodies to peptide 1147 (amino acids 1147-61) of the SARS-CoV-2 protein S are highly diagnostic. Peptide 1147, although located in a region that is partly spatially hidden in the intact protein, is not subject to mutations, suggesting therapeutic potential. The aim of this study was to elucidate the architecture of this region and the way in which it is presented to antibodies. As a model system, this peptide carrying a single lipophilic tail and the same peptide carrying a lipophilic tail at both ends (pseudocyclic) were incorporated into lipid membrane. Isolated anti-1147 antibodies interacted with it regardless of how the peptide was presented, be that freely exposed via the N-terminus, organized as a pseudocycle, or adsorbed on the surface. MDS showed that peptide 1147 is capable of closely approaching the membrane. Analysis of the surface properties of peptide 1147 in membrane-bound states and in available conformations in the full-sized S protein reveals interface for interaction with antibodies. Interestingly, the latter bears similarities to one published peptide-antibody complex. However, these antibodies, in spite of their high diagnostic significance, show no virus-neutralizing activity, indicating that peptide 1147 has no therapeutic value as a synthetic vaccine.

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Aliper, E. T., Ryzhov, I. M., Obukhova, P. S., Tuzikov, A. B., Galanina, O. E., Ziganshina, M. M., Sukhikh, G. T., Krylov, N. A., Henry, S. M., Efremov, R. G., Bovin, N. V.. 2025-03-21. Immune Antibodies Recognizing the Stem Region of SARS-CoV-2 Spike Protein: Molecular Modelling and In Vitro Study of Synthetic Peptides Presentation to the Antibodies. https://doi.org/10.1101/2025.03.20.644166

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