Evidence map›Paper›PMID 25751579›Full record

ArticleNature communications2015

Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor.

Jiří Schimer, Marcela Pávová, Maria Anders, Petr Pachl, Pavel Šácha, Petr Cígler, Jan Weber, Pavel Majer, Pavlína Řezáčová, Hans-Georg Kräusslich and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Neutral sphingomyelinase 2 is required for HIV-1 maturation.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Deactivatable Bisubstrate Inhibitors of Protein Kinases.Molecules (Basel, Switzerland) · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Optimizing the refinement of merohedrally twinned P6Acta crystallographica. Section D, Structural biology · 2020
    Article
  12. Article
  13. Article
  14. Maturation of retroviruses.Current opinion in virology · 2019
    Review
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Jiří Schimer1] Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic [2] Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43, Prague 2, Czech Republic.
Marcela PávováInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Maria AndersDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Petr PachlInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Pavel Šácha1] Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic [2] Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43, Prague 2, Czech Republic.
Petr CíglerInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Jan WeberInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Pavel MajerInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Pavlína ŘezáčováInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic.
Hans-Georg Kräusslich1] Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany [2] Molecular Medicine Partnership Unit, Heidelberg, Germany.
Barbara Müller1] Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany [2] Molecular Medicine Partnership Unit, Heidelberg, Germany.
Jan Konvalinka1] Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo n.2, 166 10, Prague 6, Czech Republic [2] Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43, Prague 2, Czech Republic.
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry · CZHeidelberg University · DECharles University · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.

Indexed as

AminocoumarinsBinding SitesCarbamatesHEK293 CellsHIV-1HIV ProteaseHIV Protease InhibitorsHumansKineticsLightModels, MolecularPhotolysisProtein BindingProtein PrecursorsProteolysisTime FactorsAminocoumarinsCarbamatesHIV ProteaseHIV Protease Inhibitorsp55 gag precursor protein, Human immunodeficiency virus 1Protein Precursorsthiazol-5-ylmethyl (5-(2-amino-3-methylbutanamido)-3-hydroxy-1,6-diphenylhexan-2-yl)carbamateValine

Identifiers

PMID25751579
PMCPMC4366505
OpenAlexW1974200353

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.