File:Fmicb-11-01063-g002.jpg

English: FIGURE 2. Structure of HIV-1 Env in the native and fusion-intermediate states, which serve as targets for protein- and peptide-based HIV inactivators. (A) Schematic representation of HIV-1 Env composition, including the surface subunit gp120 and the transmembrane subunit gp41. Key residues of CD4bs are located in the region of residues 362–372 in gp120. Amino acid residues are numbered according to those of BG505 SOSIP.664 trimer (PDB ID: 5V8M). (B) Attachment of the HIV-1 Env to the cellular receptor(s) and fusion of viral envelope with the target cell membrane. Binding of gp120 with CD4 on the target cell surface triggers conformational change of gp120 with the exposure of the CoRbs, allowing gp120 binding to its coreceptor CCR5 or CXCR4. Subsequently, gp41 changes its conformation, resulting in the insertion of fusion peptide (FP) of gp41 into the target cell membrane and formation of the pre-fusion intermediate (PFI) state. The N- and C-terminal heptad repeats (NHRs and CHRs) of the three gp41 subunits interact with each other to form a six-helix bundle (6-HB) structure, which brings the viral envelope and target cell membrane together to achieve fusion. The pre-fusion trimer is highlighted in a green box, which is shown in more detail in (C). (C) Side view of the pre-fusion, trimeric conformation of the Env present on the virion surface, which is presented as the glycan-shielded crystal structure (modified from PDB ID: 5V8M). Names and illustrations of inactivators are drawn in the three boxes, and the arrows depict their target sites, including CD4bs, CD4bs plus CoRbs or PFI induced by D1D2 binding to CD4bs.