FIG 1.

Model of cleaved and uncleaved HIV-1 Env conformational states. The native, cleaved, membrane-associated HIV-1 Env trimer is metastable, occupying an equilibrium of three conformational states that are modulated by CD4 receptor and conformation-sensitive ligands. State 1 or the “closed” conformation is predominant. CD4 receptor binding triggers State 2, an obligate intermediate. The fully “open” conformation, State 3 or the three-CD4-bound conformation, is characterized by coreceptor binding site (CoRBS) formation. State 1 is bound and stabilized by attachment inhibitors and broadly neutralizing antibodies (bNAbs) whereas States 2 and 3 are favored by CD4 mimetic compounds (CD4mc) and non-neutralizing antibodies (nNAbs). The uncleaved Env trimer is similar metastable but favors States 2 and 3. Created with Biorender.com.