tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jan 2;16(1):6.
doi: 10.1038/s41467-024-55358-9. Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy
Qingrong Zhang[SUP] 1 [/SUP], Raissa S L Rosa[SUP] 2 [/SUP], Ankita Ray[SUP] 1 [/SUP], Kimberley Durlet[SUP] 1 [/SUP], Gol Mohammad Dorrazehi[SUP] 1 [/SUP], Rafael C Bernardi[SUP] 3 4 [/SUP], David Alsteens[SUP] 5 6 [/SUP]
Affiliations
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.
. 2025 Jan 2;16(1):6.
doi: 10.1038/s41467-024-55358-9. Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy
Qingrong Zhang[SUP] 1 [/SUP], Raissa S L Rosa[SUP] 2 [/SUP], Ankita Ray[SUP] 1 [/SUP], Kimberley Durlet[SUP] 1 [/SUP], Gol Mohammad Dorrazehi[SUP] 1 [/SUP], Rafael C Bernardi[SUP] 3 4 [/SUP], David Alsteens[SUP] 5 6 [/SUP]
Affiliations
- PMID: 39747000
- DOI: 10.1038/s41467-024-55358-9
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.