Figure 6: Proposed mechanism of membrane fusion promoted by MERS-CoV S protein.

After cleavage into S1/S2 subunits, the S1 subunit is easily disassociated from the S2 subunit. In the endosome, the S2′ cleavage site could be further cleaved by the host proteases, releasing its fusion peptide. Then, under low pH environment, the connecting region, HR1 helix and central helix undergo structural rearrangement to form a long helix to help the insertion of the fusion peptide into the host membrane. Finally, the HR1 and HR2 fold into an intra-hairpin helical structure that can trimerically assemble into a six-helix bundle, resulting in membrane fusion.