Fig. 3
From: Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies
Structure of SARS-CoV-2, spike (S) protein-mediated membrane fusion, and potential therapy against the spike protein. SARS-CoV-2 comprises four structural proteins: S, M, E, and N proteins. Specifically, S protein is composed of two functional subunits, S1 subunit for attachment and S2 subunit for fusion. S1 subunit is composed of NTD and CTD. S1 subunit exerts its effects primarily through RBD in CTD. S2 subunit is made up of FP, a helix–turn–helix structure formed by HR1 and HR2 around a CH, CD, TM, and CT. SARS-CoV-2 is recognized by the binding of RBD and ACE2. Next, the S protein could be hydrolyzed by host proteases at the cleavage spots of S1/S2 (furin) and S2 (TMPRSS2). Then the conformation of S protein is irreversibly changed to further activate the release of the FP structural constraints. S2 subunit is folded to form antiparallel 6-HB by three HR2 segments folding into the grooves on the surface of the HR1 inner core, thereby resulting in the lipid membrane fusion of the virus and the host. Three drugs could fight with S protein containing vaccines and nAbs against S protein and recombinant HR1/HR2 peptides against 6-HB formation. Vaccines against S protein play their role via antigen presentation, cytokine stimulation, and antibody production, whereas nAbs directly bind to S protein to fight with it
