Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy
(2025) Nature Communications — Vol. 16, n° 1, p. 6 (2025)
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- Authors
Ray, Ankita 
Dorrazehi, Gol Mohammad
- 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.
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Citations
Zhang, Q., Rosa, R. S. L., Ray, A., Durlet, K., Dorrazehi, G. M., Bernardi, R. C., & Alsteens, D. (2025). Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy. Nature Communications, 16(1), 6. https://doi.org/10.1038/s41467-024-55358-9 (Original work published 2025)