2015 Research Highlights
The Future of HIV-1 Therapeutics: Resistance is Futile?
A review of current and future approaches to treatment of HIV-1.
Torbet, B. E., Goodsell, D. S. & Richman, D. D., eds.
Curr. Top. Microbiol. Immunol. 389 (2015).
Chapters from HIVE Center members:
Forli, S. & Olson, A. J. Computational Challenges of Structure-Based Approaches Applied to HIV. PMID 25711462.
Feng, L., Larue, R. C., Slaughter, A., Kessl, J. J. & Kvaratskhelia, M. HIV-1 Integrase Multimerization as a Therapeutic Target. PMID 25778682.
Mori, M., Kovalenko, L., Lyonnais, S., Antaki, D. Torbett, B. E., Motta, M., Mirambeau, G. & Mely, Y. Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1. PMID 25749978.
Goodsell, D. S. Illustrations of the HIV Life Cycle. PMID 25716304.
HIV life cycle illustrations from the issue are available on in the Resources section of the HIVE Center site.
Alpha-carboxy nucleoside phosphonates as universal nucleoside triphosphate mimics
A new nucleotide scaffold was designed for use in inhibiting DNA polymerases and other targets.
Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening against the Flap Site of HIV Protease
The Binding Energy Distribution Analysis Method improves discrimination of binders and nonbinders in virtual screening results against HIV protease.
Deep Sequencing of Protease Inhibitor Resistant HIV Patient Isolates Reveals Patterns of Correlated Mutations in Gag and Protease
Deep sequencing of viruses from 93 patients has revealed mutations in Gag proteins contribute to recurrent treatment failure.
Distribution and redistribution of HIV-1 nucleocapsid in immature, mature, and integrase-inhibited virions: a role for integrase in maturation
An important role of integrase in packaging of the HIV-1 genome is revealed.
PubMed PMID: 26178982
PubMed Central PMCID: PMC4577894
Asynchronous replica exchange software for grid and heterogenous computing
Methods for performing molecular dynamics simulations on large clusters of computers are presented.
PubMed PMID: 27103749
PubMed Central PMCID: PMC4834714
Differential isotopic enrichment to facilitate characterization of asymmetric multimeric proteins using hydrogen/deuterium exchange mass spectrometry
By labeling the two subunits of reverse transcriptase with different isotopes of nitrogen, the subunits may be distinguished in hydrogen/deuterium exchange experiments.
X-ray structures of native HIV-1 capsid protein reveal conformational variability
A crystallographic structure of full-length HIV-1 capsid shows new variability in capsid assembly.
Pronounced inhibition shift from HIV reverse transcriptase to herpetic DNA polymerases by increasing the flexibility of alpha-carboxy nucleotide phosphates.
A new class of polymerase inhibitors is tuned to target different viruses.
PubMed PMID: 26450273
PubMed Central PMCID: PMC4893804
CellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology
A new method for creating 3D models of cellular systems is applied to the analysis of envelope glycoprotein distribution in HIV.
HCV glycoprotein structures: what to expect from the unexpected
Recent structural insights into the envelope glycoproteins of hepatitis C virus are reviewed.
Khan AG, Miller MT, Marcotrigiano J Curr Opin Virol 12, 53-58 (2015).
Structural basis of clade-specific HIV-1 neutralization by humanized anti-V3 monoclonal antibody KD-247
Structure of an antibody that binds to HIV envelope glycoprotein reveals an unusual mode of interaction centered around the light chain of the antibody.
Fast hepatitis C virus RNA elimination and NS5A redistribution by NS5A inhibitors studied by multiplex assay approach
A new method is presented to assess the effectiveness of novel inhibitors of hepatitis C virus.
PubMed PMID: 25845863
PubMed Central PMCID: PMC4432190
Synthesis and properties of 2′-deoxy-2′,4′-difluoroarabinose-modified nucleic acids
A modified nucleoside is used to build RNA strands that are more resistant to degradation, for use in gene silencing applications.
New structure sheds light on selective HIV-1 genomic RNA packaging
HIVE members review current work probing the structure and function of the HIV genome.
Olson ED, Cantara WA & Musier-Forsyth K. Viruses 7, 4826-4835 (2015)
PubMed PMID: 26305251
PubMed Center PMCID: PMC4576207
CoVaMa: Co-variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data
A new method has been developed to analyze linked variations in large sequence datasets from viral populations.
Routh A, Chang MW, Okulicz JF, Johnson JE & Torbett BE. Methods 91, 40-47 (2015)
PubMed PMID: 26408523
PubMed Central PMCID: PMC4684750
Structural integrity of the ribonuclease H domain in HIV-1 reverse transcriptase
The role of several mutations in the folding of reverse transcriptase is revealed.
PubMed PMID: 26061827
PubMed Central PMCID: PMC4509971
Design, synthesis, biochemical, and antiviral evaluations of C6 benzyl and C6 biarylmethyl substituted 2-hydroxylisoquinoline-1,3-diones: dual inhibition agains HIV reverse transcriptase-associated RNase H and polymerase with antiviral activities
Inhibitors that block the RNase H site of reverse transcriptase have been discovered.
PubMed PMID: 25522204
PubMedCentral PMCID: PMC4306517
Role of the mammalian target of rapamycin pathway in lentiviral vector transduction of hematopoietic stem cells
Rapamycin improves lentiviral delivery of genes to hematopoietic stem cells.
Wang CX & Torbett BE. Curr Opin Hematol 22, 302-308 (2015)
PubMed Central PMCID: PMC4688901
Large-scale asynchronous and distributed multidimensional replical exchange molecular simulations and efficiency analysis
New methods are developed for rapid molecular dyamics simulations on large clusters of computers.
Xia J, Flynn WF, Gallicchio E, Zhang BW, He P, Tan Z & Levy RM. J Comput Chem 36, 1772-1785 (2015)
PubMed Central PMCID: PMC4512903
