Figure 1

HIV entry and its inhibition. In the native conformation of Env, a canopy of three gp120 molecules (green) covers gp41, holding the trimer in a metastable conformation. Binding to cellular lectins (black) keeps Env close to the cellular membrane, facilitating subsequent interactions with CD4 (orange) and a chemokine receptor (CoR, purple). These gp120/receptor interactions trigger gp41 to extend and insert its N-terminal fusion peptide segment (red) into the target cell membrane. Ultimately, the exposed heptad repeat segments in the N- and C-terminal regions of the gp41 ectodomain [labeled N (gray) and C (blue)] associate to form the trimer-of-hairpins structure, juxtaposing viral and cellular membranes in a manner crucial for membrane fusion. HIV entry inhibitors investigated as potential topical prevention strategies are listed in red below each modeled transition.