Results 21 to 30 of about 989 (99)

Multimodal mechanism of action of allosteric HIV-1 integrase inhibitors [PDF]

Expert Reviews in Molecular Medicine, 2013
Integrase (IN) is required for lentivirus replication and is a proven drug target for the prevention of AIDS in HIV-1-infected patients. While clinical strand transfer inhibitors disarm the IN active site, allosteric inhibition of enzyme activity through the disruption of IN–IN protein interfaces holds great therapeutic potential.
Kellie A. Jurado, Alan Engelman
openaire   +4 more sources

Development of an AlphaScreen-Based HIV-1 Integrase Dimerization Assay for Discovery of Novel Allosteric Inhibitors [PDF]

SLAS Discovery, 2012
In recent years, HIV-1 integrase (IN) has become an established target in the field of antiretroviral drug discovery. However, its sole clinically approved inhibitor, the integrase strand transfer inhibitor (INSTI) raltegravir, has a surprisingly low genetic barrier for resistance.
Demeulemeester, J., Tintori, C., Botta, Maurizio, Debyser, Z., Christ, F.   +4 more
openaire   +4 more sources

Computational and synthetic approaches for developing Lavendustin B derivatives as allosteric inhibitors of HIV-1 integrase [PDF]

European Journal of Medicinal Chemistry, 2016
Through structure-based virtual screening and subsequent activity assays of selected natural products, Lavendustin B was previously identified as an inhibitor of HIV-1 integrase (IN) interaction with its cognate cellular cofactor, lens epithelium-derived growth factor (LEDGF/p75).
Maria Rosa Buemi, James R. Fuchs, Stefania Ferro, Fatima E. Agharbaoui, Fatima E. Agharbaoui, Rosaria Gitto, Laura De Luca, Mamuka Kvaratskhelia, Ashley C. Hoyte   +8 more
openaire   +3 more sources

TALEN Knockout of the PSIP1 Gene in Human Cells: Analyses of HIV-1 Replication and Allosteric Integrase Inhibitor Mechanism [PDF]

Journal of Virology, 2014
ABSTRACT HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and integration cofactor. The LEDGF/p75 gene, PSIP1 , is a potential therapeutic target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4 + T cells, and knockout mice have normal ...
Hind J. Fadel, Eric M. Poeschla, James H. Morrison, Mamuka Kvaratskhelia, Dyana T. Saenz, Stephen C. Ekker, James R. Fuchs   +6 more
openaire   +4 more sources

Allosteric HIV Integrase Inhibitors Promote Formation of Inactive Branched Polymers via Homomeric Carboxy-Terminal Domain Interactions [PDF]

Structure, 2021
The major effect of allosteric HIV integrase (IN) inhibitors (ALLINIs) is observed during virion maturation, where ALLINI treatment interrupts IN-RNA interactions via drug-induced IN aggregation, leading to the formation of aberrant virions. To understand the structural changes that accompany drug-induced aggregation, we determined the soft matter ...
Kushol Gupta, Audrey Allen, Carolina Giraldo, Grant Eilers, Robert Sharp, Young Hwang, Hemma Murali, Katrina Cruz, Paul Janmey, Frederic Bushman, Gregory D. Van Duyne   +10 more
openaire   +4 more sources

Structure-function analyses unravel distinct effects of allosteric inhibitors of HIV-1 integrase on viral maturation and integration [PDF]

Journal of Biological Chemistry, 2018
Recently, a new class of HIV-1 integrase (IN) inhibitors with a dual mode of action, called IN-LEDGF/p75 allosteric inhibitors (INLAIs), was described. Designed to interfere with the IN-LEDGF/p75 interaction during viral integration, unexpectedly, their major impact was on virus maturation.
Bonnard, Damien, Le Rouzic, Erwann, Eiler, Sylvia, Amadori, Céline, Orlov, Igor, Bruneau, Jean-Michel, Brias, Julie, Barbion, Julien, Chevreuil, Francis, Spehner, Daniele, Chasset, Sophie, Ledoussal, Benoit, Moreau, François, Saib, Ali, Klaholz, Bruno, P., Emiliani, Stéphane, Ruff, Marc, Zamborlini, Alessia, Benarous, Richard   +18 more
openaire   +7 more sources

The A128T Resistance Mutation Reveals Aberrant Protein Multimerization as the Primary Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors [PDF]

Journal of Biological Chemistry, 2013
Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a very promising new class of anti-HIV-1 agents that exhibit a multimodal mechanism of action by allosterically modulating IN multimerization and interfering with IN-lens epithelium-derived growth factor (LEDGF)/p75 binding.
Feng, Lei, Sharma, Amit, Slaughter, Alison, Jena, Nivedita, Koh, Yasuhiro, Shkriabai, Nikolozi, Larue, Ross C., Patel, Pratiq A., Mitsuya, Hiroaki, Kessl, Jacques J., Engelman, Alan, Fuchs, James R., Kvaratskhelia, Mamuka   +12 more
openaire   +5 more sources

A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain [PDF]

Journal of Biological Chemistry, 2016
HIV-1 integrase (IN) is essential for virus replication and represents an important multifunctional therapeutic target. Recently discovered quinoline-based allosteric IN inhibitors (ALLINIs) potently impair HIV-1 replication and are currently in clinical trials.
Patel, Disha, Antwi, Janet, Koneru, Pratibha, Serrao, Erik, Forli, Stefano, Kessl, Jacques, Feng, Lei, Deng, Nanjie, Levy, Ronald, Fuchs, James, Olson, Arthur, Engelman, Alan, Bauman, Joseph, Kvaratskhelia, Mamuka, Arnold, Eddy   +14 more
openaire   +5 more sources

Molecular Modeling Study on the Allosteric Inhibition Mechanism of HIV-1 Integrase by LEDGF/p75 Binding Site Inhibitors

PLoS ONE, 2014
HIV-1 integrase (IN) is essential for the integration of viral DNA into the host genome and an attractive therapeutic target for developing antiretroviral inhibitors. LEDGINs are a class of allosteric inhibitors targeting LEDGF/p75 binding site of HIV-1 IN.
Xiao-Jun Yao, Weiwei Xue, Huanxiang Liu
openaire   +6 more sources

Synthesis of an HIV-1 Integrase Allosteric Site Inhibitor [PDF]

Synfacts, 2019
Philip Kocieński
openaire   +3 more sources