Related Experiment Video
Updated: Jul 20, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Determinants of activity of the HIV-1 maturation inhibitor PA-457
Feng Li1, Dorian Zoumplis, Claudia Matallana
1Panacos Pharmaceuticals, 209 Perry Parkway, Gaithersburg, MD 20877, USA.
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.
Related Concept Videos
Inhibitors of Virion Maturation and Assembly
Retrovirus Life Cycles
Inhibitors of Viral Protein Synthesis

