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Pratibha C. Koneru
University of Colorado Denver
Viral replicationIntegraseAllosteric regulationIntegrase inhibitorBiology
13Publications
5H-index
60Citations
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Publications 13
Newest
#1Francesca Esposito (University of Cagliari)H-Index: 19
#2Mario Sechi (University of Sassari)H-Index: 27
Last. Enzo Tramontano (University of Cagliari)H-Index: 31
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 L Elliott (WashU: Washington University in St. Louis)H-Index: 2
#2Jenna E. Eschbach (WashU: Washington University in St. Louis)
Last. Sebla B. Kutluay (WashU: Washington University in St. Louis)H-Index: 12
view all 10 authors...
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...
Source
#1Pratibha C. Koneru (CU: University of Colorado Boulder)H-Index: 5
#2Ashwanth C. Francis (Emory University)H-Index: 5
Last. Mamuka Kvaratskhelia (CU: University of Colorado Boulder)H-Index: 35
view all 15 authors...
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...
4 CitationsSource
#1Pratibha C. Koneru (CU: University of Colorado Boulder)H-Index: 5
#2Ashwanth C. Francis (Emory University)H-Index: 5
Last. Mamuka Kvaratskhelia (CU: University of Colorado Boulder)H-Index: 35
view all 15 authors...
Source
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...
Source
#1Tyler A. Wilson (OSU: Ohio State University)H-Index: 2
#2Pratibha C. Koneru (University of Colorado Denver)H-Index: 5
Last. James R. Fuchs (OSU: Ohio State University)H-Index: 23
view all 10 authors...
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...
1 CitationsSource
#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: 36
view all 8 authors...
: The internal N6-methyladenosine (m6A) modification of cellular mRNA regulates post-transcriptional gene expression. The YTH domain family proteins (YTHDF1-3 or Y1-3) bind to m6A-modified cellular mRNAs and modulate their metabolism and processing, thereby affecting cellular protein translation. We previously reported that HIV-1 RNA contains the m6A modification and that Y1-3 proteins inhibit HIV-1 infection by decreasing HIV-1 reverse transcription activity. Here, we investigated the mechanism...
18 CitationsSource
#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: 36
view all 7 authors...
The internal N6-methyladenosine (m6A) modification of cellular mRNA regulates post-transcriptional gene expression. The YTH domain family proteins (YTHDF1-3, or Y1-3 for short) bind to m6A-modified cellular mRNA and modulate its metabolism and processing, thereby affecting protein translation in cells. We previously reported that HIV-1 RNA contains m6A modification and that Y1-3 proteins inhibit HIV-1 infection by decreasing HIV-1 reverse transcription. Here we extended our studies to better und...
1 CitationsSource
#1Ashley C. Hoyte (University of Colorado Denver)H-Index: 4
#2Augusta V. Jamin (Harvard University)H-Index: 3
Last. Mamuka Kvaratskhelia (University of Colorado Denver)H-Index: 35
view all 8 authors...
Abstract The pyridine-based multimerization selective HIV-1 integrase (IN) inhibitors (MINIs) are a distinct subclass of allosteric IN inhibitors. MINIs potently inhibit HIV-1 replication during virion maturation by inducing hyper- or aberrant IN multimerization but are largely ineffective during the early steps of viral replication. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116...
5 CitationsSource
#1Michaela K. Madison (WashU: Washington University in St. Louis)H-Index: 1
#2Dana Q. Lawson (WashU: Washington University in St. Louis)H-Index: 1
Last. Sebla B. Kutluay (WashU: Washington University in St. Louis)H-Index: 12
view all 9 authors...
: 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. These particles are noninfectious and are blocked at an early reverse transcription stage in target cells. However, the basis of this reverse transcription defect is unknown. Here, we sho...
9 CitationsSource
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