Disseminating the HIV Fusion Mechanism: gp41 Structural Details in Membranes

Molecular dynamics simulation of HIV-1 fusion domain-membrane complexes: Insight into the N-terminal gp41 fusion mechanism.

To understand how viral proteins fuse with the cell membrane, a process that is important for the initial stages of infection, the conformation of the membrane-bound viral fusion peptides (FPs) must be identified. Here, molecular dynamics (MD) simulations were performed to investigate the conformation of the FP-16 and FP-23 of human immunodeficiency virus (HIV) bound to a dimyristoyl phosphatid...

HIV gp41 trimer mimics for vaccines and fusion inhibitors

Asymmetric Deactivation of HIV-1 gp41 following Fusion Inhibitor Binding

Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env) that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env intera...

Identification of a Human Protein-Derived HIV-1 Fusion Inhibitor Targeting the gp41 Fusion Core Structure

The HIV-1 envelope glycoprotein (Env) gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR) of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no...

Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound ...