Evidence map›Paper›PMID 31653397›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine.

Ilker Kudret Sariyer, Jennifer Gordon, Tricia H Burdo, Hassen S Wollebo, Eleonora Gianti, Martina Donadoni, Anna Bellizzi, Stephanie Cicalese, Regina Loomis, Jake A Robinson and 7 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.International journal of molecular sciences · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Empirical Treatment and Prevention of COVID-19.Infection & chemotherapy · 2020
    Review
  11. Article
  12. Repurposing an HIV Drug for Zika Virus Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Ilker Kudret SariyerDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Jennifer GordonDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Tricia H BurdoDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Hassen S WolleboDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Eleonora GiantiDepartment of Chemistry, Institute for Computational Molecular Science, College of Science and Technology, Temple University, 1901 N. 12(th) Street, Philadelphia, PA 19122, USA.
Martina DonadoniDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Anna BellizziDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Stephanie CicaleseDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Regina LoomisDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Jake A RobinsonDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Vincenzo CarnevaleDepartment of Chemistry, Institute for Computational Molecular Science, College of Science and Technology, Temple University, 1901 N. 12(th) Street, Philadelphia, PA 19122, USA.
Joseph SteinerTranslational Neuroscience Center, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Mehmet H OzdenerMonell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Andrew D MillerCollege of Veterinary Medicine, Cornell University, T5-006A Veterinary Research Tower, Ithaca, NY 14853, USA.
Shohreh AminiDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Michael L KleinDepartment of Chemistry, Institute for Computational Molecular Science, College of Science and Technology, Temple University, 1901 N. 12(th) Street, Philadelphia, PA 19122, USA.
Kamel KhaliliDepartment of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address: kamel.khalili@temple.edu.
Temple University · USCornell University · USMonell Chemical Senses Center · USNational Institute of Neurological Disorders and Stroke · US

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Ilker Kudret Sariyer · 2011 to 2026
$24.9M
Interdisciplinary And Translational Research Training In NeurohivT32MH079785 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Kamel Khalili · 2008 to 2026
$5.4M
NIMH NIH HHS P30 MH092177NIMH NIH HHS T32 MH079785
6 · The paper itself

Abstract

Zika virus (ZIKV) infection is associated with microcephaly in neonates and Guillain-Barré syndrome in adults. ZIKV produces a class of nonstructural (NS) regulatory proteins that play a critical role in viral transcription and replication, including NS5, which possesses RNA-dependent RNA polymerase (RdRp) activity. Here we demonstrate that rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1 infection, inhibits the enzymatic activity of NS5 and suppresses ZIKV infection and replication in primary human astrocytes. Similarly, other members of the NNRTI family, including etravirine and efavirenz, showed inhibitory effects on viral infection of brain cells. Site-directed mutagenesis identified 14 amino acid residues within the NS5 RdRp domain (AA265-903), which are important for the RPV interaction and the inhibition of NS5 polymerase activity. Administration of RPV to ZIKV-infected interferon-alpha/beta receptor (IFN-A/R) knockout mice improved the clinical outcome and prevented ZIKV-induced mortality. Histopathological examination of the brains from infected animals revealed that RPV reduced ZIKV RNA levels in the hippocampus, frontal cortex, thalamus, and cerebellum. Repurposing of NNRTIs, such as RPV, for the inhibition of ZIKV replication offers a possible therapeutic strategy for the prevention and treatment of ZIKV-associated disease.

Indexed as

AnimalsAnti-HIV AgentsBrainHumansMiceMice, KnockoutMutagenesis, Site-DirectedMutationProtein BindingProtein ConformationReceptor, Interferon alpha-betaRilpivirineViral Nonstructural ProteinsVirus ReplicationZika VirusZika Virus InfectionAnti-HIV AgentsNS5 protein, flavivirusReceptor, Interferon alpha-betaRilpivirineViral Nonstructural Proteinsanimal modelastrocytesNS5rilpivirineZika virus

Identifiers

PMID31653397
PMCPMC6904669
OpenAlexW2980153752

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.