Liu Keliang

The peptides and peptidomimetics: HIV-1 fusion inhibitors

The fusion of HIV and target cell membranes is mediated by the transmembrane glycoprotein gp41. HIV-1 fusion inhibitors target gp41 to prevent the virus-cell membrane fusion, thus interrupt the initial steps of viral replication. The first peptide fusion inhibitor (T-20) was approved by the U.S. FDA in 2003. However, the application of T-20 was limited by drawbacks such as rapid proteolysis, highly clinical dosage, poor patient adhesive and ineffectiveness to drug resistant HIV-1 isolates. In recent years, considerable progresses have been made in the understanding of the mechanism of fusion inhibitors and in the design of novel fusion inhibitors, to overcome the drawbacks of T-20. Various peptides and peptidomimetics used as fusion inhibitors have been developed, and these novel fusion inhibitors target different part of HIV-1 gp41 and show higher activity and better pharmacokinetic properties. In this paper, the recent progresses in the design and development of novel peptides and peptidominetics used as HIV-1 fusion inhibitors are reviewed, providing a reference for related drug development and basic research.