Evidence map›Paper›PMID 32442424›Full record

ArticleCell chemical biology2020

Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism.

Qi Liu, Amita Gupta, Ayse Okesli-Armlovich, Wenjie Qiao, Curt R Fischer, Mark Smith, Jan E Carette, Michael C Bassik, Chaitan Khosla

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. A SARS-CoV-2 antiviral therapy score card.Global health & medicine · 2020
    Article
  11. Article
  12. Article
  13. 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

9 authors at 1 institution in 1 country.

Qi LiuDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
Amita GuptaStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Ayse Okesli-ArmlovichDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
Wenjie QiaoDepartment of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Curt R FischerStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
Mark SmithStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA.
Jan E CaretteStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Michael C BassikStanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Chaitan KhoslaDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA. Electronic address: khosla@stanford.edu.
Stanford University · US

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
Genetic screens to find critical host factors for SARS-CoV-2 infectionR01AI140186 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2019 to 2023
$2.3M
Host Genes Critical for Flavivirus InfectionR01AI141970 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2019 to 2023
$2.0M
NIAID NIH HHS R01 AI140186NIAID NIH HHS R01 AI141970NIAID NIH HHS U19 AI109662
6 · The paper itself

Abstract

Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors.

Indexed as

AnimalsAntiviral AgentsCarbazolesCells, CulturedChlorocebus aethiopsDengue VirusEnzyme InhibitorsFemaleHumansMaleMicrobial Sensitivity TestsMolecular StructurePyrimidinesRNA-Dependent RNA PolymeraseUridineVirus ReplicationAntiviral AgentsCarbazolesEnzyme InhibitorsN-((1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl)-2-pyridinecarboxamidePyrimidinesRNA-Dependent RNA PolymeraseUridineantiviral therapycombinationcytidine monophosphate kinasedenguedihydroorotate dehydrogenasepyrimidine metabolismRNA-dependent RNA polymeraseuridine-cytidine kinase

Identifiers

PMID32442424
PMCPMC7241336
OpenAlexW3028150847

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.