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Mamuka Kvaratskhelia
University of Colorado Boulder
IntegraseMolecular biologyDNABiochemistryBiology
105Publications
34H-index
2,834Citations
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Publications 107
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#1Francesca Esposito (University of Cagliari)H-Index: 18
#2Mario Sechi (University of Sassari)H-Index: 26
Last. Enzo Tramontano (University of Cagliari)H-Index: 28
view all 15 authors...
Abstract The management of Human Immunodeficiency Virus type 1 (HIV-1) infection requires life-long treatment that is associated with chronic toxicity and possible selection of drug-resistant strains. A new opportunity for drug intervention is offered by antivirals that act as allosteric inhibitors targeting two viral functions (dual inhibitors). In this work, we investigated the effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) derivatives on both HIV-1 Integrase (IN) and Reverse Transcr...
2 CitationsSource
#1Jennifer Elliott (WashU: Washington University in St. Louis)H-Index: 3
Last. Sebla B. KutluayH-Index: 13
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A large number of HIV-1 integrase (IN) alterations, referred to as class II substitutions, exhibit pleotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of three distinct mechanisms: i) markedly reducing IN levels thus precluding formation of IN complexes with viral RNA; ii) adversely affecting functional IN multimerization a...
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#1Pratibha C. Koneru (CU: University of Colorado Boulder)H-Index: 4
#2Ashwanth C. Francis (Emory University)H-Index: 5
Last. Mamuka Kvaratskhelia (CU: University of Colorado Boulder)H-Index: 34
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HIV-1 inserts its genetic code into human genomes, turning healthy cells into virus factories. To do this, the virus uses an enzyme called integrase. Front-line treatments against HIV-1 called “integrase strand-transfer inhibitors” stop this enzyme from working. These inhibitors have helped to revolutionize the treatment of HIV/AIDS by protecting the cells from new infections. But, the emergence of drug resistance remains a serious problem. As the virus evolves, it changes the shape of its integ...
2 CitationsSource
#1Pratibha C. Koneru (CU: University of Colorado Boulder)H-Index: 4
#2Ashwanth C. Francis (Emory University)H-Index: 5
Last. Mamuka Kvaratskhelia (CU: University of Colorado Boulder)H-Index: 34
view all 15 authors...
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#1Jacob Al-Saleem (OSU: Ohio State University)H-Index: 4
#2Wessel P. Dirksen (OSU: Ohio State University)H-Index: 12
Last. Patrick L. Green (OSU: Ohio State University)H-Index: 29
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An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replicatio...
2 CitationsSource
#2Matthew J. KobeH-Index: 3
Last. Mamuka KvaratskheliaH-Index: 34
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#1Tyler A. Wilson (OSU: Ohio State University)H-Index: 2
#2Pratibha C. Koneru (University of Colorado Denver)H-Index: 4
Last. James R. Fuchs (OSU: Ohio State University)H-Index: 22
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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-shaped pocket at the IN dimer interface and is highly selective for promoting higher-order multimerization of inactive IN over inhibiting IN-LEDG...
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#1Elisa RivieccioH-Index: 1
#2Luciana TartaglioneH-Index: 26
Last. Michela VarraH-Index: 16
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Abstract Some G-quadruplex (GQ) forming aptamers, such as T30695, exhibit particularly promising properties among the potential anti-HIV drugs. T30695 G-quadruplex binds to HIV-1 integrase (IN) and inhibits its activity during 3′-end processing at nanomolar concentrations. Herein we report a study concerning six T30695-GQ variants, in which the R or S chiral glycerol T, singly replaced the thymine residues at the T30695 G-quadruplex loops. CD melting, EMSA and HMRS experiments provided informati...
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#1Wuxun Lu (OSU: Ohio State University)H-Index: 2
#2Nagaraja Tirumuru (OSU: Ohio State University)H-Index: 3
Last. Li Wu (OSU: Ohio State University)H-Index: 34
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8 CitationsSource
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