2019 Research Highlights
Alpha-carboxynucleoside phosphonates: direct-acting inhibitors of viral DNA polymerases
A new class of polymerase inhibitors mimic nucleotide triphosphates
PubMed PMID: 30648904
PubMedCentral PMCID: PMC6362432
The GTPase domain of MX2 interacts with the HIV-1 capsid, enabling its short isoform to moderate antiviral restriction
Restriction factor MX2 interacts with HIV-1 capsid through multiple contacts
PubMed PMID: 31722207
PubMedCentral PMCID: PMC7391006
Epistasis and entrenchment of drug resistance in HIV-1 subtype B
HIVE researchers explore how viral populations mutate when treated with antiviral drugs.
Biswas A, Haldane A, Arnold E, Levy RM. Elife. 2019 Oct 8;8.
PubMed PMID: 31591964
PubMedCentral PMCID: PMC6783267
Intrinsic conformational dynamics of the HIV-1 genomic RNA 5’UTR
FRET experiments explore the complex higher-order structure of the HIV-1 genome.
PubMed PMID: 31068467
PubMedCentral PMCID: PMC6534999
Epstein-Barr virus BORF2 inhibits cellular APOBEC3B to preserve viral genome integrity
Epstein-Barr virus, the causative agent of infectious mononucleosis and multiple cancers, utilizes a two-pronged approach to counteract restriction by APOBEC3B
PubMed PMID: 30420783
PubMedCentral PMCID: PMC6294688
Novel Intersubunit Interaction Critical for HIV-1 Core Assembly Defines a Potentially Targetable Inhibitor Binding Pocket
A new site for inhibition of HIV-1 capsid is explored.
PubMed PMID: 30862755
PubMedCentral PMCID: PMC6414707
Structure of HIV-1 RT/dsRNA initiation complex prior to nucleotide incorporation
HIVE Center members reveal the structure of a complex that mimics the reverse transcription initiation complex.
Das K, Martinez SE, DeStefano JJ, Arnold E. Proc Natl Acad Sci U S A 116, 7308-7313 (2019).
PubMed PMID: 30902895
PubMedCentral PMCID: PMC6462067
Comparison of affinity ranking using AutoDock-GPU and MM-GBSA scores for BACE-1 inhibitors in the D3R Grand Challenge 4
Estimates of surface area in affinity prediction are evaluated in a docking challenge.
PubMed PMID: 31691919
PubMedCentral PMCID: PMC7027993
Integrative modeling of the HIV-1 ribonucleoprotein complex
Coarse-grain models explore the complex of HIV-1 genomic RNA with integrase and nucleocapsid.
Goodsell DS, Jewett A, Olson AJ, Forli S. PLoS Comput Biol. 2019 Jun 13;15(6):e1007150.
PubMed PMID: 31194731
PubMedCentral PMCID: PMC6592547
Cryo-EM Structures of a Group II Intron Reverse Splicing into DNA
Cryoelectron microscopy captures the atomic details of group II introns in action.
Haack DB, Yan X, Zhang C, Hingey J, Lyumkis D, Baker TS, Toor N. Cell. 2019 178(3):612-623.
PubMed PMID: 31348888
PubMedCentral PMCID: PMC6662634
Influence of multiple-sequence-alignment depth on Potts statistical models of protein covariation
HIVE Center researchers explore how the characteristics of a data set effect the results of Potts covariation analysis.
Haldane A, Levy RM. Phys Rev E 99:032405 (2019).
PubMed PMID: 30999494
PubMed Central PMCID: PMC6508952
Strain-specific effect on biphasic DNA binding by HIV-1 integrase
HIV-1 integrase binds to DNA in high-affinity and low-affinity modes.
PubMed PMID: 30475264
PubMedCentral PMCID: PMC6472922
Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification
New chemoenzymatic methods are developed for modifying glycans, to explore glycan-mediated entry of viruses.
PubMed PMID: 30996301
PubMedCentral PMCID: PMC6470217
Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication
Transfer RNA plays key roles in the life cycle of retroviruses.
Jin D, Musier-Forsyth K. J Biol Chem. 294, 5352-5364 (2019).
PubMed PMID: 30700559
PubMedCentral PMCID: PMC6462514
HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors
Effective new allosteric integrase inhibitors have been discovered.
PubMed PMID: 31120420
PubMedCentral PMCID: PMC6581505
Visualization of positive and negative sense viral RNA for probing the mechanism of direct-acting antivirals against hepatitis C virus
New methods reveal the distribution of positive-strand and negative-strand viral RNA in living cells.
PubMed PMID: 31717338
PubMedCentral PMCID: PMC6893808
Challenges and opportunities in cryo-EM single-particle analysis
Cryoelectron microscopy is providing new opportunities for discovery and exploration of biomolecular structure.
Lyumkis D. J Biol Chem. 294, 5181-5197 (2019).
PubMed PMID: 30804214
PubMedCentral PMCID: PMC6442032
Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes
Methods for lentiviral-mediated gene therapy are improved by temporary coapplication of a cyclic resveratrol trimer.
PubMed PMID: 31416800
PubMedCentral PMCID: PMC6888140
Determining 3′-termini and sequences of nascent single-stranded viral DNA molecules during HIV-1 reverse transcription in infected cells
New methods for monitoring of nucleic acid intermediates during virus replication are presented
Pollpeter D, Sobala A, Malim MH. J Vis Exp. 2019 Jan 30;(143):10.3791/58715.
PubMed PMID: 30774124
PubMedCentral PMCID: PMC6682491
Structural studies and biological evaluation of T30695 variants modified with single chiral glycerol-T reveal the importance of LEDGF/p75 for the aptamer anti-HIV-integrase activities
Aptamers are developed to probe the allosteric properties of HIV-1 integrase
PubMed PMID: 30414444
HIV-1 Vif triggers cell cycle arrest by degrading cellular PPP2R5 phospho-regulators
HIV-1 stops infected cells from dividing by degrading regulatory proteins with the accessory protein Vif
PubMed PMID: 31665623
PubMedCentral PMCID: PMC6903395
D3R Grand Challenge 4: prospective pose prediction of BACE1 ligands with AutoDock-GPU
A GPU-accelerated AutoDock is benchmarked in a docking challenge.
PubMed PMID: 31691920
Conformational Changes in HIV-1 Reverse Transcriptase that Facilitate Its Maturation
The surprising role of transfer RNA in the maturation of HIV-1 reverse transcriptase is explored.
PubMed PMID: 31471129
PubMedCentral PMCID: PMC6774901
An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors
New ALLINIs are discovered using an isoquinoline scaffold.
PubMed PMID: 30783506
PubMed Central PMCID: PMC6378678
Massive-Scale Binding Free Energy Simulations of HIV Integrase Complexes Using Asynchronous Replica Exchange Framework Implemented on the IBM WCG Distributed Network
Very large computational screens of HIV integrase inhibitorsNew are performed using distributed computing.
PubMed PMID: 30758197
PubMedCentral PMCID: PMC6496938
Structure-guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG-I
RNA molecules are tuned for activity against a potential target for vaccination and immunotherapy.
Yong HY, Zheng J, Ho VCY, Nguyen MT, Fink K, Griffin PR, Luo D. FEBS Lett. 2019 593(21):3003-3014.
PubMed PMID: 31369683
Analysis of discrete local variability and structural covariance in macromolecular assemblies using Cryo-EM and focused classification
Focused classification is shown to be a powerful method for determining structures of flexible biomolecules.
PubMed PMID: 30528101
PubMedCentral PMCID: PMC6476647
SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase
SuFEx compounds can target specific proteins and form covalent complexes.
PubMed PMID: 31484779
PubMedCentral PMCID: PMC6754619
