Evidence map›Paper›PMID 36434067›Full record

ArticleCommunications biology2022

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.

Mohammad W Bahar, Veronica Nasta, Helen Fox, Lee Sherry, Keith Grehan, Claudine Porta, Andrew J Macadam, Nicola J Stonehouse, David J Rowlands, Elizabeth E Fry and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Mohammad W BaharDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK. mohammad.bahar@strubi.ox.ac.uk.ORCID 0000-0002-2350-2682
Veronica NastaDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK.
Helen FoxThe National Institute for Biological Standards and Control, Potters Bar, EN6 3QG, UK.
Lee SherryAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0002-4367-772X
Keith GrehanAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0003-3976-756X
Claudine PortaDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK.
Andrew J MacadamThe National Institute for Biological Standards and Control, Potters Bar, EN6 3QG, UK.ORCID 0000-0002-8687-1573
Nicola J StonehouseAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0003-1146-5519
David J RowlandsAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0002-4742-9272
Elizabeth E FryDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK.ORCID 0000-0001-9754-5303
David I StuartDivision of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, OX3 7BN, UK. dave.stuart@strubi.ox.ac.uk.ORCID 0000-0002-3426-4210
Centre for Human Genetics · GBUniversity of Leeds · GBNational Institute for Biological Standards and Control · GBThe Pirbright Institute · GB

Funding

Biotechnology and Biological Sciences Research CouncilDepartment of HealthGates Foundation RG.IMCB.I8-TSA-083Medical Research Council MC_PC_17137Medical Research Council MR/N00065X/1Medical Research Council MR/V001329/1Wellcome Trust 060208/Z/00/ZWellcome Trust 093305/Z/10/ZWellcome Trust 101122/Z/13/ZWellcome Trust 203141/Z/16/Z
6 · The paper itself

Abstract

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

Indexed as

EnterovirusPoliovirusVaccines, Virus-Like ParticleAntigens, ViralAntiviral AgentsBenzeneBinding SitesGlutathioneSulfonamidesAntigens, ViralAntiviral AgentsBenzeneGlutathioneSulfonamidesVaccines, Virus-Like Particle

Identifiers

PMID36434067
PMCPMC9700776
OpenAlexW4310056568

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.