Structure-Based Adaptation of a SARS-CoV-2 Neutralizing Peptide to New Virus Variants

Raasch N, Weißenborn L, Richel E, Schäfer S, Denysenko O, Bartelsen N, Sticht H, Überla K, Eichler J (2026)


Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 69

Pages Range: 17845-17853

Journal Issue: 15

DOI: 10.1021/acs.jmedchem.5c03311

Abstract

The starting point of this work was a SARS-CoV-2 neutralizing peptide (LW25.13), which binds to the receptor-binding domain of the viral spike protein and inhibits the attachment of the virus to its cellular receptor ACE2. As LW25.13 is unable to neutralize later SARS-CoV-2 variants, such as omicron, we have extended the neutralization breadth of LW25.13 through structural and bioinformatic analysis. This involved the systematic variation of a range of positions and yielded peptides neutralizing SARS-CoV-2 beta and omicron at low nanomolar concentrations, while preserving the strong neutralizing capacity against earlier virus variants (wild-type, alpha, delta), as well as the proteolytic stability and α-helical conformation of the peptide. This gain in neutralizing breadth illustrates the utility of the peptide as a scaffold that can be adapted to different virus variants, which may prove useful for the development of peptides against new coronavirus variants of concern in the future.

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How to cite

APA:

Raasch, N., Weißenborn, L., Richel, E., Schäfer, S., Denysenko, O., Bartelsen, N.,... Eichler, J. (2026). Structure-Based Adaptation of a SARS-CoV-2 Neutralizing Peptide to New Virus Variants. Journal of Medicinal Chemistry, 69(15), 17845-17853. https://doi.org/10.1021/acs.jmedchem.5c03311

MLA:

Raasch, Nina, et al. "Structure-Based Adaptation of a SARS-CoV-2 Neutralizing Peptide to New Virus Variants." Journal of Medicinal Chemistry 69.15 (2026): 17845-17853.

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