The SARS-CoV-2 spike protein’s membrane-binding domain bridges the viral and host cell membrane, a critical step in triggering membrane fusion. 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. We observe that the disulfide bridge stabilizes the MBP’s interaction with the membrane, suggesting a structural role in viral entry.