2013 Research Highlights
Detecting allosteric sites of HIV-1 reverse transcriptase by X-ray crystallographic fragment screening
New sites for the design of inhibitors are discovered throughout the structure of HIV RT.
PubMed PMID: 23342998
PubMedCentral PMCID: PMC3906421
Rapid deep sequencing of patient-derived HIV with ion semiconductor technology
Ion Torrent devices are used for deep sequencing of drug resistant HIV samples, yielding high levels of sequencing coverage in HIV Gag and protease, and allowing the detection of mutations at low frequencies.
Chang MW, Oliveira G, Yuan J, Okulicz JF, Levy S, Torbett BE. J Virol Methods. 189(1):232-4 (2013).
HIV-1 reverse transcriptase and antiviral drug resistance
A discussion of the current state of understanding of RT structure and function, and mechanisms of drug resistance.
Part 1: Das K & Arnold E. Curr. Op. Virol. 3, 119-128 (2013)
PubMed PMID: 23602471
PMCID: PMC4097814
Part 2: Das K & Arnold E. Curr. Op. Virol. 3, 119-128 (2013)
PubMed PMID: 23602470
PubMedCentral PMCID: PMC4097817
Allosteric Inhibition of HIV-1 Integrase Activity
A review of progress with the development of allosteric integrase inhibitors (ALLINIs) that compete with LEDGF/p75 for binding to integrase, disrupting viral maturation and inhibiting integrase function.
Engelman, A., Kessl, J. J. & Kvaratskhelia, M. Curr. Op. Chem. Biol. 17, 339-345 (2013)
The A128T Resistance Mutation Reveals Aberrant Protein Multimerization as the Primary Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors
A new resistance mutation in HIV integrase reveals an unexpected mechanism for action for integrase inhibitors.
Evaluation of Combinations of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine with Clinically Used Antiretroviral Drugs
The potent antiviral activity of EfdA is found to be synergistic with rilpivirine.
Multimodal mechanism of action of allosteric HIV-1 integrase inhibitors
A review of the action of ALLINIs and their use in study of integrase function in the HIV life cycle.
Jurado KA & Engelman A. Expert Rev. Mol. Med. 15, e14 (2014).
PubMed PMID: 24274067
PMCID: PMC3919682
Allosteric Integrase Inhibitor Potency is Determined Through the Inhibition of HIV-1 Particle Maturation
Allosteric integrase inhibitors, originally developed to block viral integration, are also surprisingly found to be potent inhibitors of viral maturation.
Effects of Substitutions at the 4′ and 2 Positions on the Bioactivity of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine
The structural basis of the potent antiviral activity of EFdA is revealed.
Snapshot of the equlibrium dynamics of a drug bound to HIV-1 reverse transcriptase
Spectroscopy, crystallography and computer simulation are used to probe the dynamics of HIV RT when interacting with rilpivirine.
PubMed PMID: 23422558
PubMedCentral PMCID: PMC3607437
Hypersusceptibility Mechanism of Tenofovir-Resistant HIV to EFdA
A significant decrease in excision efficiency makes EFdA effective against drug resistant HIV RT.
AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug screening
HIVE researchers have developed software that automates the entire process of crystallographic fragment screening for the discovery of inhibitors.
PubMed PMID: 23633588
PubMedCentral PMCID: PMC3640469
Viral precursor polypeptides: key of regulation from replication to maturation
Four recent structures of viral polyprotein precursors are reviewed.
Yost SA & Marcotrigiano J. Curr. Op. Virol. 3, 137-142 (2013).
PubMed PMID: 23602469
PubMedCentral PMCID: PMC3660988
