Evidence map›Paper›PMID 18715909›Full record

ArticleJournal of virology2008

Identification of a broad-spectrum arenavirus entry inhibitor.

Ryan A Larson, Dongcheng Dai, Virginia T Hosack, Ying Tan, Tove' C Bolken, Dennis E Hruby, Sean M Amberg

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

89 citing papers in PubMed, 141 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Entry inhibitors as arenavirus antivirals.Frontiers in microbiology · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Lassa Virus Countermeasures.Current topics in microbiology and immunology · 2023
    Article

29 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Ryan A LarsonSIGA Technologies, Inc., Corvallis, Oregon 97333, USA.
Dongcheng Dai
Virginia T Hosack
Ying Tan
Tove' C Bolken
Dennis E Hruby
Sean M Amberg
Siga Technologies (United States) · US

Funding

Antiviral Drugs for Lassa Fever VirusR44AI056525 · NIAID · SIGA TECHNOLOGIES, INC. · PI AMBERG, SEAN M · 2004 to 2008
$11.3M
Antiviral Drugs Against Hemorrhagic Fever VirusesR43AI056525 · NIAID · VIROPHARMA, INC. · PI COLLETT, MARC S · 2003 to 2003
$910k
NIAID NIH HHS R43 R44 AI056525NIAID NIH HHS R44 AI056525
6 · The paper itself

Abstract

Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral activity identified a modified structure, ST-193, with a 50% inhibitory concentration (IC(50)) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes as well, including the remaining four commonly associated with hemorrhagic fever (IC(50)s for Junín, Machupo, Guanarito, and Sabiá were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 microM. Determinants of ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed mutagenesis. Taken together, these studies demonstrate that sensitivity to ST-193 is dictated by a segment of about 30 amino acids within the GP2 subunit. This region includes the carboxy-terminal region of the ectodomain and the predicted transmembrane domain of the envelope protein, revealing a novel antiviral target within the arenavirus envelope GP.

Indexed as

Amino Acid SequenceAntiviral AgentsArenavirusBenzimidazolesBinding SitesInhibitory Concentration 50Molecular StructureMutagenesis, Site-DirectedSequence AlignmentViral Envelope ProteinsVirus InternalizationAntiviral AgentsBenzimidazolesViral Envelope Proteins

Identifiers

PMID18715909
PMCPMC2573164
OpenAlexW2008110867

What OpenQuestion holds

Textmetadata
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.