2021 Research Highlights

Evaluating local and directional resolution of cryo-EM density maps

Methods are presented for evaluating and improving cryo-EM maps.

Aiyer S, Zhang C, Baldwin PR, Lyumkis D. Methods Mol Biol. 2021;2215:161-187.

PubMed PMID: 33368004

Tools for visualizing and analyzing Fourier space sampling in Cryo-EM

Tools are presented for understanding how molecular orientation impacts structure determination by cryoelectron microscopy.

Baldwin PR, Lyumkis D. Prog Biophys Mol Biol. 2021 Mar;160:53-65.

PubMed PMID: 32645314

PubMedCentral PMCID: PMC7785567 (available on )

Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia

Avoiding drug resistance in HIV reverse transcriptase

HIVE Center researchers review the biology of HIV reverse transcriptase and discuss approaches to fight drug resistance.

Cilento ME, Kirby KA, Sarafianos SG.  Chem Rev. 2021 Mar 24;121(6):3271-3296.

PubMed PMID: 33507067

PubMedCentral PMCID: PMC8149104 (available on 2022-03-24)

Revealing the structural plasticity of SARS-CoV-2 nsp7 and nsp8 using structural proteomics

Solution-based structural proteomics techniques reveal that two coronavirus non-structural proteins may form multiple oligomeric states.

Courouble VV, Dey SK, Yadav R, Timm J, Harrison JJEK, Ruiz FX, Arnold E, Griffin PR. J Am Soc Mass Spectrom. 2021 Jul 7;32(7):1618-1630.

PubMed PMID: 34121407

PubMedCentral PMCID: PMC8231661

Discrimination between functional and non-functional cellular Gag complexes involved in HIV-1 assembly

The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr

Researchers explore how HIV protein Vpr blocks the natural defenses against integration of the viral genome.

Dupont L, Bloor S, Williamson JC, Cuesta SM, Shah R, Teixeira-Silva A, Naamati A, Greenwood EJD, Sarafianos SG, Matheson NJ, Lehner PJ. Cell Host Microbe. 2021 May 12;29(5):792-805.

PubMed PMID: 33811831

PubMedCentral PMCID: PMC8118623

MrHAMER yields highly accurate single molecule viral sequences enabling analysis of intra-host evolution

A new nanopore-based method allows long-range sequencing of thousands of viral genomes from clinical samples.

Gallardo CM, Wang S, Montiel-Garcia DJ, Little SJ, Smith DM, Routh AL, Torbett BE.  Nucleic Acids Res. 2021 Jul 9;49(12):e70.

PubMed PMID: 33849057

PubMedCentral PMCID: PMC8266615

Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Mi3-GPU: MCMC-based Inverse Ising Inference on GPUs for protein covariation analysis

HIVE Center members improve methods for predicting interactions between amino acids based on observed mutational covariations.

Haldane A, Levy RM. Comput Phys Commun. 2021 Mar;260:107312.

PubMed PMID: 33716309

PubMedCentral PMCID: PMC7944406 (available on 2022-03-01)

Icosahedral virus structures and the Protein Data Bank

The history of structural studies of icosahedral viruses is reviewed.

Johnson JE, Olson AJ.  J Biol Chem. 2021 Jan-Jun;296:100554.

PubMed PMID: 33744290

PubMedCentral PMCID: PMC8081926

Sec24C is an HIV-1 host dependency factor crucial for virus replication

HIV-1 integrase inhibitors with modifications that affect their potencies against drug resistant integrase mutants

Based on structures of HIV-1 and SIV integrases, new integrase strand transfer inhibitors are designed and tested for their ability to block drug-resistant mutants of the enzyme.

Smith SJ, Zhao XZ, Passos DO, Pye VE, Cherepanov P, Lyumkis D, Burke TR Jr, Hughes SH. ACS Infect Dis. 2021 Jun 11;7(6):1469-1482.

PubMed PMID: 33686850

PubMedCentral PMCID: PMC8205226

Integrase strand transfer inhibitors are effective anti-HIV drugs

Clinically-useful inhibitors that block the active site of HIV-1 integrase are reviewed.

Smith SJ, Zhao XZ, Passos DO, Lyumkis D, Burke TR Jr, Hughes SH.  Viruses. 2021 Jan 29;13(2):205.

PubMed PMID: 33572956

PubMedCentral PMCID: PMC7912079

Computational design of small molecular modulators of protein-protein interactions with a novel thermodynamic cycle: Allosteric inhibitors of HIV-1 integrase

A new method for targeting protein-protein interfaces is applied to design of integrase inhibitors

Sun Q, Ramaswamy VSK, Levy R, Deng N. Protein Sci. 2021 Feb;30(2):438-447.

PubMed PMID: 33244804

PubMedCentral PMCID: PMC7784772

Cleavage and Polyadenylation Specificity Factor 6 is required for efficient HIV-1 latency reversal

The cellular protein CPSF6 plays a novel role in HIV-1 transcription and latency of the virus.

Zheng Y, Schubert HL, Singh PK, Martins LJ, Engelman AN, D’Orso I, Hill CP, Planelles V.  mBio. 2021 Jun 29;12(3):e0109821.

PubMed PMID: 34154414

Interactions of HIV-1 Capsid with host factors and their implications for developing novel therapeutics

The structure and function of HIV-1 capsid and its interactions with host factors and drugs are reviewed.

Zhuang S, Torbett BE. Viruses. 2021 Mar 5;13(3):417.

PubMed PMID: 33807824

PubMedCentral PMCID: PMC8001122