Spike glycoprotein of Middle East respiratory syndrome-related coronavirus (MERS-CoV S protein) (MERS-CoV S (Spike))

The spike glycoprotein of Middle East respiratory syndrome-related coronavirus (MERS-CoV) is a trimeric, heavily glycosylated class I viral fusion protein on the virion surface that mediates host-cell entry. Each protomer comprises an S1 subunit containing the N-terminal domain (NTD) and a C-terminal receptor-binding domain (RBD), and an S2 subunit containing the fusion peptide, heptad repeats (HR1, HR2), transmembrane domain, and cytoplasmic tail. The RBD specifically binds the host receptor CD26/dipeptidyl peptidase 4 (DPP4), enabling viral attachment and triggering conformational changes that, upon proteolytic activation at S1/S2 and S2′ sites, drive membrane fusion via a six-helix bundle formed by HR1 and HR2. The spike exhibits dynamic RBD conformations (“lying” and “standing”) that regulate receptor accessibility, and its dense N-linked glycans contribute to folding, receptor/attachment interactions (including sialosides via NTD), and immune evasion. Owing to its essential role in entry and surface exposure, the MERS-CoV spike is a central therapeutic and vaccine target for neutralizing antibodies, fusion-inhibitory peptides, and strategies that stabilize the prefusion conformation.

Other names

Spike protein of MERS-CoVS glycoproteinEnvelope spike proteinMERS-CoV spikeMERS spikeS1 subunitS2 subunitReceptor-binding domain (RBD) of MERS-CoV spikeN-terminal domain (NTD) of MERS-CoV spike

Neutralizing antibodies block RBD binding to CD26/DPP4 or lock prefusion conformations to prevent fusion; HR1/HR2-derived peptides disrupt six-helix bundle formation, preventing membrane fusion; Protease inhibitors prevent S1/S2 or S2′ cleavage, blocking activation for fusion