Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer

  • Nat Chem Biol. 2010 Dec;6(12):887-9. doi: 10.1038/nchembio.456.
Lisa M Miller Jenkins  1 ,  David E Ott ,  Ryo Hayashi ,  Lori V Coren ,  Deyun Wang ,  Qun Xu ,  Marco L Schito ,  John K Inman ,  Daniel H Appella ,  Ettore Appella
Affiliations
  • 1. Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
PMID: 20953192 DOI: 10.1038/nchembio.456
Abstract

The zinc fingers of the HIV-1 nucleocapsid protein, NCp7, are prime targets for antiretroviral therapeutics. Here we show that S-acyl-2-mercaptobenzamide thioester (SAMT) chemotypes inhibit HIV by modifying the NCp7 region of Gag in infected cells, thereby blocking Gag processing and reducing infectivity. The thiol produced by SAMT reaction with NCp7 is acetylated by cellular Enzymes to regenerate active SAMTs via a recycling mechanism unique among small-molecule inhibitors of HIV.

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