Synthesized Peptide Inhibitors of HIV-1 gp41-dependent Membrane Fusion

Author(s): Yuxian He.

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 10 , 2013

Abstract:

Fusion of viral and cellular membranes is an essential step for HIV-1 infection. This process offers an attractive target for developing antiviral agents. T20 (Enfuvirtide, Fuzeon), a 36-amino acid peptide derived from the C-terminal heptad repeat region of HIV-1 gp41, is the first and only clinically approved HIV-1 fusion inhibitor that being used for treatment of HIV/AIDS patients failed to respond to current antiretroviral drugs. However, T20-resistance can be acquired rather easily in vitro and in vivo. T1249 is considered as a representative of the second generation fusion inhibitors, but its clinical evaluation was halted due to the problem of drug formulation. To overcome these challenges, a number of strategies have been applied to develop the third or next-generation inhibitors with the significantly improved antiviral activity and pharmacokinetic profiles. Promisingly, several peptides are currently under clinical trials, such as Sifuvirtide and VIR-576. Recently, several high resolution crystal structures of HIV-1 fusion inhibitor peptides were reported, which reveal the key residues or motifs underlying their potency against diverse HIV-1 variants. This review highlights the development of the representative peptide inhibitors of HIV-1 fusion toward providing some insights into the future of this class of anti-HIV drugs.

Keywords: HIV-1, membrane fusion, antivirals, peptide inhibitor

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Article Details

VOLUME: 19
ISSUE: 10
Year: 2013
Page: [1800 - 1809]
Pages: 10
DOI: 10.2174/1381612811319100004

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