SARS-CoV-2 fusion peptide (FP)

The SARS-CoV-2 fusion peptide is a short, highly conserved hydrophobic segment (~23 residues, typically spanning S816–G838, N-terminus of S2’ after cleavage) within the S2 subunit of the spike (S) glycoprotein[5][4][9]. This peptide is essential for mediating the fusion of viral and host membranes during viral entry. Upon receptor binding and proteolytic activation, the fusion peptide undergoes conformational rearrangement and inserts into the host cell membrane, triggering the merger of viral and cellular lipid bilayers[4][1][9]. Its structure is partly α-helical and forms a wedge or hairpin that can deeply insert and perturb the host membrane, being stabilized by hydrophobic interactions, a fusion-active core (notably residues L821, L822, F823), and sometimes a disulfide-bonded loop immediately downstream (fusion loop or FPPR)[2][4][5]. It is a validated, conserved target for antiviral drugs and neutralizing antibodies, with both research peptides and monoclonal antibodies shown to interfere with its function and reduce viral infectivity, making it a promising target for next-generation COVID-19 therapeutics and vaccines[6][7][4][5].

Other names

Spike fusion peptideS2 fusion peptideSARS-CoV-2 S fusion peptideFusion domain

Inhibition of membrane fusion by blocking the fusion peptide’s interaction with the host cell membrane; Steric hindrance of S2’ proteolytic site, preventing activation of fusion process; Direct neutralization by antibody binding to the fusion peptide epitope, blocking conformational changes required for fusion