Effects of an HIV-1 maturation inhibitor on the structure and dynamics of CA-SP1 junction helices in virus-like particles

Significance Compounds known as “maturation inhibitors” are potentially important treatments for HIV-1 infections. These compounds strongly inhibit the conversion of immature HIV-1 virions to the mature, infectious state by blocking an essential step in the cleavage of the Gag polyprotein of immature virions into its individual protein subunits. We show that the mechanism of action of the prototype maturation inhibitor bevirimat involves surprisingly subtle changes in molecular structure and molecular motions at the critical cleavage site within the Gag polyprotein lattice of the immature state. Results from these experiments, in which a variety of solid-state nuclear magnetic resonance techniques are applied to virus-like particles prepared in vitro, may contribute to the further development of effective maturation inhibitors.