Results 11 to 20 of about 1,267 (159)

Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase

Antimicrobial Agents and Chemotherapy, 2023
HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on the viral protein with the host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of HIV-1 IN protein to severely perturb maturation of viral particles.
Damien Bonnard, Erwann Le Rouzic, Matthew R. Singer, Zhe Yu, Frédéric Le Strat, Claire Batisse, Julien Batisse, Céline Amadori, Sophie Chasset, Valerie E. Pye, Stéphane Emiliani, Benoît Ledoussal, Marc Ruff, F. Moreau, Peter Cherepanov, Richard Benarous   +15 more
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Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3′-Processing Suppression [PDF]

Pharmaceuticals
Background: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also
Sharif Karim Sayyed, Marzuqa Quraishi, D. S. Prabakaran, Balaji Chandrasekaran, Thiyagarajan Ramesh, Satish Kumar Rajasekharan, Chaitany Jayprakash Raorane, Tareeka Sonawane, Vinothkannan Ravichandran   +8 more
doaj   +2 more sources

Multimode, Cooperative Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors [PDF]

Journal of Biological Chemistry, 2012
The multifunctional HIV-1 enzyme integrase interacts with viral DNA and its key cellular cofactor LEDGF to effectively integrate the reverse transcript into a host cell chromosome. These interactions are crucial for HIV-1 replication and present attractive targets for antiviral therapy.
Jacques J. Kessl, Nivedita Jena, Yasuhiro Koh, Humeyra Taskent‐Sezgin, Alison Slaughter, Lei Feng, Suresh de Silva, Li Wu, Stuart F.J. Le Grice, Alan Engelman, James R. Fuchs, Mamuka Kvaratskhelia   +11 more
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Allosteric HIV-1 Integrase Inhibitors Lead to Premature Degradation of the Viral RNA Genome and Integrase in Target Cells [PDF]

Journal of Virology, 2017
ABSTRACT Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice.
Michaela K. Madison, Dana Q. Lawson, Jennifer L. Elliott, Ayşe Naz Ozantürk, Pratibha C. Koneru, Dana Townsend, M. Errando, Mamuka Kvaratskhelia, Sebla B. Kutluay   +8 more
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The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity [PDF]

Retrovirology, 2017
Background HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration.
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P. Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous   +23 more
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HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-[1-(1-benzyl-1H-pyrazol-4-yl)-3-(3,4-dihydro-2H-1-benzopyran-6-yl)isoquinolin-4-yl](tert-butoxy)acetic acid [PDF]

ACS Medicinal Chemistry Letters, 2018
Allosteric HIV-1 integrase inhibitors (ALLINIs) are a new class of potential antiretroviral therapies with a unique mechanism of action and drug resistance profile. To further extend this class of inhibitors via a scaffold hopping approach, we have synthesized a series of analogues possessing an isoquinoline ring system. Lead compound 6l binds in the v-
Tyler A. Wilson, Pratibha C. Koneru, Stephanie Rebensburg   +2 more
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The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome. [PDF]

PLoS ONE, 2014
The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75.
Nikki van Bel, Yme van der Velden, Damien Bonnard, Erwann Le Rouzic, Atze T Das, Richard Benarous, Ben Berkhout   +6 more
doaj   +3 more sources

Indole-based allosteric inhibitors of HIV-1 integrase [PDF]

Bioorganic & Medicinal Chemistry Letters, 2016
Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket.
Pratiq A. Patel, Nina Kvaratskhelia, Yara E. Mansour, Janet Antwi, Lei Feng, Pratibha C. Koneru, Mathew J. Kobe, Nivedita Jena, Guqin Shi, Mosaad S. Mohamed, Chenglong Li, Jacques J. Kessl, James R. Fuchs   +12 more
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Structural Impact of Ex Vivo Resistance Mutations on HIV-1 Integrase Polymers Induced by Allosteric Inhibitors

Journal of Molecular Biology
HIV-1 integrase (IN) is targeted by two classes of antivirals: integrase strand transfer inhibitors (INSTIs), which bind to the active site within the catalytic core domain (CCD), and allosteric integrase inhibitors (ALLINIs), which bind at the CCD dimer interface. ALLINIs were initially designed to disrupt interactions with the cellular cofactor LEDGF/
Saira Montermoso, Grant Eilers, Audrey Allen, R. Sharp, Young Kyu Hwang, Frederic D. Bushman, Kushol Gupta, Gregory Van Duyne   +7 more
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Allosteric HIV Integrase Inhibitors Promote Formation of Inactive Branched Polymers via Homomeric Carboxy-Terminal Domain Interactions [PDF]

Structure, 2020
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 Díaz Giraldo, Grant Eilers, Robert Sharp, Young Sun Hwang, Hemma Murali, Katrina Cruz, Paul A. Janmey, Frederic D. Bushman, Gregory D. Van Duyne   +10 more
openalex   +4 more sources