HIV Research Today is a free monthly online journal that collates and summarizes the latest research about HIV, including details on human immunodeficiency virus, testing, treatment, prevention, vaccines, aids. | ||||||||
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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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