Evidence map›Paper›PMID 30974762›Full record

ArticleViruses2019

Mechanism of Action of Methotrexate Against Zika Virus.

Sungjun Beck, Zhe Zhu, Michelli F Oliveira, Davey M Smith, Jeremy N Rich, Jean A Bernatchez, Jair L Siqueira-Neto

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Viruses, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05300009 (Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts), which is not on this map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.2field-weighted citation impact, top 3% 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.

NCT05300009 naunknown statusnot on this mapstarted 2022, after this paper: background citation

Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts : A Prospective Controlled Randomized Trial

TypeinterventionalSponsorAssiut UniversityRan2022 to 2023Enrolled68ConditionsWartsArmstopical methotrexate hydrogel 1% coupled with microneedling., Liquid nitrogen
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Advancement in the Development of Therapeutics Against Zika Virus Infection.Frontiers in cellular and infection microbiology · 2022
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Sungjun BeckSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. sjbeck@ucsd.edu.
Zhe ZhuSanford Consortium for Regenerative Medicine, La Jolla, CA 92093, USA. zhz504@ucsd.edu.ORCID 0000-0002-5385-948X
Michelli F OliveiraDepartment of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92093, USA. mfariadeoliveira@ucsd.edu.
Davey M SmithDepartment of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92093, USA. d13smith@ucsd.edu.
Jeremy N RichSanford Consortium for Regenerative Medicine, La Jolla, CA 92093, USA. drjeremyrich@gmail.com.ORCID 0000-0001-7845-5302
Jean A BernatchezSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. jbernatchez@ucsd.edu.ORCID 0000-0002-8309-1627
Jair L Siqueira-NetoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. jairlage@ucsd.edu.
University of California San Diego · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4M
Mentoring Translational Research in HIVK24AI100665 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SMITH, DAVID MITCHELL · 2012 to 2021
$1.5M
NCATS NIH HHS UL1 TR001442NIAID NIH HHS K24 AI100665NIAID NIH HHS P30 AI036214
6 · The paper itself

Abstract

Zika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barré syndrome, reemerged as a serious public health threat in Latin America in recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), which is clinically used as an anti-cancer chemotherapy and anti-rheumatoid agent. We studied the mechanism of action of MTX against ZIKV in relation to its inhibition of dihydrofolate reductase (DHFR) in vitro using Vero and human neural stem cells (hNSCs). As expected, an antiviral effect for MTX against ZIKV was observed, showing up to 10-fold decrease in virus titer during MTX treatment. We also observed that addition of leucovorin (a downstream metabolite of DHFR pathway) rescued the ZIKV replication impaired by MTX treatment in ZIKV-infected cells, explaining the antiviral effect of MTX through inhibition of DHFR. We also found that addition of adenosine to ZIKV-infected cells was able to rescue ZIKV replication inhibited by MTX, suggesting that restriction of de novo synthesis adenosine triphosphate (ATP) pools suppresses viral replication. These results confirm that the DHFR pathway can be targeted to inhibit replication of ZIKV, similar to other published results showing this effect in related flaviviruses.

Indexed as

AdenosineAnimalsAntiviral AgentsCells, CulturedFolic Acid AntagonistsHumansLeucovorinMethotrexateNeural Stem CellsViral LoadVirus ReplicationZika VirusAdenosineAntiviral AgentsFolic Acid AntagonistsLeucovorinMethotrexateantiviralsdihydrofolate reductasemethotrexatenucleotide metabolismZika virus

Identifiers

PMID30974762
PMCPMC6521145
OpenAlexW2949736083

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.