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A peptide inhibitor of HIV-1 assembly in vitro.

Sticht J, Humbert M, Findlow S, Bodem J, Müller B, Dietrich U, Werner J, Kräusslich HG

Department of Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.

Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.

Published 3 August 2005 in Nat Struct Mol Biol, 12(8): 671-7.
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