Zhang, Q., Rosa, R.S.L., Ray, A. orcid.org/0000-0002-5059-9598 et al. (4 more authors) (2025) Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy. Nature Communications, 16 (1). 6. ISSN 2041-1723
Abstract
The SARS-CoV-2 spike protein’s membrane-binding domain bridges the viral and host cell membrane, a critical step in triggering membrane fusion. Here, we investigate how the SARS-CoV-2 spike protein interacts with host cell membranes, focusing on a membrane-binding peptide (MBP) located near the TMPRSS2 cleavage site. Through in vitro and computational studies, we examine both primed (TMPRSS2-cleaved) and unprimed versions of the MBP, as well as the influence of its conserved disulfide bridge on membrane binding. Our results show that the MBP preferentially associates with cholesterol-rich membranes, and we find that cholesterol depletion significantly reduces viral infectivity. Furthermore, we observe that the disulfide bridge stabilizes the MBP’s interaction with the membrane, suggesting a structural role in viral entry. Together, these findings highlight the importance of membrane composition and peptide structure in SARS-CoV-2 infectivity and suggest that targeting the disulfide bridge could provide a therapeutic strategy against infection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2024. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | Spike Glycoprotein, Coronavirus; Humans; SARS-CoV-2; Cell Membrane; Microscopy, Atomic Force; Protein Binding; Cholesterol; Serine Endopeptidases; COVID-19; Virus Internalization; Disulfides; Peptides; Single Molecule Imaging |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2025 10:25 |
Last Modified: | 31 Jan 2025 10:25 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-024-55358-9 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222558 |