TY - JOUR
T1 - Determinants of activity of the HIV-1 maturation inhibitor PA-457
AU - Li, F
AU - Zoumplis, D
AU - Matallana, C
AU - Kilgore, N.R.
AU - Reddick, M
AU - Yunus, A.S.
AU - Adamson, Catherine Sarah
AU - Salzwedel, K
AU - Martin, D.E.
AU - Allaway, G.P.
AU - Freed, E.O.
AU - Wild, C.T.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750990206&partnerID=8YFLogxK
UR - http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXR-4KPP43G-1&_user=1026342&_coverDate=12%2F20%2F2006&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050565&_version=1&_urlVersion=0&_userid=1026342&md5=dc8a5c2ca0bab679be24ca3542268191
U2 - doi:10.1016/j.virol.2006.07.023
DO - doi:10.1016/j.virol.2006.07.023
M3 - Article
SN - 0042-6822
VL - 356
SP - 217
EP - 224
JO - Virology
JF - Virology
IS - 1-2
ER -
