Determinants of activity of the HIV-1 maturation inhibitor PA-457

Feng Li, Dorian Zoumplis, Claudia Matallana, Nicole R. Kilgore, Mary Reddick, Abdul S. Yunus, Catherine S. Adamson, Karl Salzwedel, David E. Martin, Graham P. Allaway, Eric O. Freed, Carl T. Wild

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

3-O-(3′,3′-dimethylsuccinyl) betulinic acid, also termed PA-457 or DSB, is a novel HIV-1 inhibitor that blocks virus maturation by disrupting cleavage of the capsid precursor, CA-SP1. To better define the molecular target for PA-457, we prepared a panel of mutant viruses with point deletions spanning the CA-SP1 cleavage domain and characterized each of these viruses for PA-457 sensitivity. Our results indicate that amino acid residues in the N-terminal half of SP1 serve as determinants of PA-457 activity, while residues in the C-terminal half of SP1 were not involved in compound activity. These findings support and extend previous observations that PA-457 is a specific inhibitor of CA-SP1 cleavage and identify the CA-SP1 domain as the primary viral determinant for this novel inhibitor of HIV-1 replication.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalVirology
Volume356
Issue number1-2
DOIs
StatePublished - Dec 5 2006

Bibliographical note

Funding Information:
This work was supported, in part, by Public Health Service Grant 5 R44 AI051047-03 to G.P.A. from the National Institutes of Health, National Institute for Allergy and Infectious Disease.

Keywords

  • CA-SP1 cleavage
  • HIV
  • Maturation inhibitor
  • PA-457
  • Viral determinants

ASJC Scopus subject areas

  • Virology

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