Middle East respiratory syndrome coronavirus spike glycoprotein S2 subunit (MERS-CoV S2)

The Middle East respiratory syndrome coronavirus (MERS-CoV) spike glycoprotein S2 subunit is a structural protein essential for the viral entry process into host cells. While the S1 subunit facilitates initial attachment to the host receptor dipeptidyl peptidase 4 (DPP4), the S2 subunit mediates the subsequent fusion of the viral envelope with the host cell membrane (PubMed: 24109236). This fusion is driven by a dramatic conformational rearrangement where the heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains interact to form a stable six-helix bundle (6-HB), bringing the viral and cellular membranes into close proximity for pore formation (PubMed: 24478444). Because the S2 subunit is more conserved than the S1 subunit across different coronavirus strains, it serves as an attractive target for broad-spectrum antiviral therapies and universal vaccine designs (PubMed: 30936361). Current drug development efforts focus on fusion-inhibitory peptides, such as HR2P and the pan-coronavirus inhibitor EK1, which mimic the HR2 domain to competitively block the formation of the 6-HB and effectively neutralize the virus (PubMed: 31015315, PubMed: 32239163).

Other names

MERS-CoV S2 proteinSpike protein S2 subunitFusion protein subunitMERS-CoV S protein S2 subunit

Inhibition of viral-host membrane fusion by binding to the heptad repeat 1 (HR1) domain of the S2 subunit, thereby preventing the formation of the six-helix bundle (6-HB) required for viral entry (PubMed: 24478444, PubMed: 30936361).