L'644

L'644 is a peptide-based HIV-1 fusion inhibitor developed by Merck Research Laboratories. It is a 36-amino acid peptide derived from the C-terminal heptad repeat (CHR) region of the HIV-1 envelope glycoprotein gp41. L'644 functions by binding to the N-terminal heptad repeat (NHR) of gp41, thereby preventing the formation of the six-helix bundle required for viral-cell membrane fusion. The compound has been extensively evaluated in preclinical studies as a potential topical microbicide candidate to prevent the sexual transmission of HIV-1. Research has demonstrated its potent antiviral activity across various mucosal tissue models, including cervical, colorectal, and penile explants, where it was often compared to other fusion inhibitors like enfuvirtide (T-20) and T-1249.