SARS-CoV-2 spike protein fusion peptide (SARS-CoV-2 S FP)

The SARS-CoV-2 spike protein fusion peptide (FP) is a highly conserved, essential region within the S2 subunit of the viral spike glycoprotein (UniProt P0DTC2). Its primary biological function is to mediate the fusion between the viral envelope and the host cell membrane, a critical step for viral entry and the release of the viral genome (nih.gov, 2023). Upon receptor binding and proteolytic priming at the S2' site (residue 816), the spike protein undergoes a dramatic conformational change that exposes the fusion peptide, allowing it to insert into the host membrane (nih.gov, 2023; Pharmacy Times, 2023). This insertion is often facilitated by interactions with host membrane lipids such as phosphatidylserine and is influenced by local pH and calcium levels (nih.gov, 2024). Because the fusion peptide is vital for infectivity and remains highly conserved across variants, it is a major target for broad-spectrum antiviral development (News-Medical, 2023). Therapeutic candidates include fusion-inhibiting peptides like PN19 and small molecules such as chlorcyclizine and umifenovir, which aim to block the fusion process and prevent the formation of syncytia (ResearchGate, 2023; MDPI, 2021; asm.org, 2022).

Other names

SARS-CoV-2 S2 fusion peptideSARS-CoV-2 spike fusion peptideInternal fusion peptideS2' fusion peptideSARS-CoV-2 spike fusion peptide region

Fusion inhibition by binding to the fusion peptide or its hydrophobic pocket, thereby preventing membrane insertion and the subsequent formation of the six-helix bundle (6-HB) required for viral-host membrane fusion (nih.gov, 2021; asm.org, 2022).