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

doi:10.1016/j.virol.2006.07.023

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 journal › Article › peer-review

62 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 language	English
Pages (from-to)	217-224
Number of pages	8
Journal	Virology
Volume	356
Issue number	1-2
DOIs	https://doi.org/10.1016/j.virol.2006.07.023
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.virol.2006.07.023

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title = "Determinants of activity of the HIV-1 maturation inhibitor PA-457",

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.",

keywords = "CA-SP1 cleavage, HIV, Maturation inhibitor, PA-457, Viral determinants",

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

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.",

year = "2006",

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doi = "10.1016/j.virol.2006.07.023",

language = "English",

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T1 - Determinants of activity of the HIV-1 maturation inhibitor PA-457

AU - Li, Feng

AU - Zoumplis, Dorian

AU - Matallana, Claudia

AU - Kilgore, Nicole R.

AU - Reddick, Mary

AU - Yunus, Abdul S.

AU - Adamson, Catherine S.

AU - Salzwedel, Karl

AU - Martin, David E.

AU - Allaway, Graham P.

AU - Freed, Eric O.

AU - Wild, Carl T.

N1 - 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.

PY - 2006/12/5

Y1 - 2006/12/5

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.

KW - CA-SP1 cleavage

KW - HIV

KW - Maturation inhibitor

KW - PA-457

KW - Viral determinants

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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