Evidence map›Paper›PMID 32868923›Full record

ArticleNature microbiology2020

Fluoxazolevir inhibits hepatitis C virus infection in humanized chimeric mice by blocking viral membrane fusion.

Christopher D Ma, Michio Imamura, Daniel C Talley, Adam Rolt, Xin Xu, Amy Q Wang, Derek Le, Takuro Uchida, Mitsutaka Osawa, Yuji Teraoka and 12 more

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022
    Article
  8. Thiophen urea derivatives as a new class of hepatitis C virus entry inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2021
    Article
  9. Review
  10. Article
  11. 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

22 authors at 3 institutions in 2 countries.

Christopher D MaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4520-5849
Michio ImamuraDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Daniel C TalleyDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Adam RoltLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Xin XuDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Amy Q WangDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Derek LeLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Takuro UchidaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Mitsutaka OsawaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Yuji TeraokaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Kelin LiCenter for Integrative Chemical Biology and Drug Discovery, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Xin HuDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Seung Bum ParkLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Nishanth ChalasaniLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Parker H IrvinLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Andres E DulceyDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Noel SouthallDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Juan J MaruganDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Zongyi HuLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Kazuaki ChayamaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Kevin J FrankowskiCenter for Integrative Chemical Biology and Drug Discovery, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7173-6352
Tsanyang Jake LiangLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. jliang@nih.gov.ORCID http://orcid.org/0000-0003-3828-702X
National Institutes of Health · USHiroshima University · JPUniversity of North Carolina at Chapel Hill · US

Funding

University of Kansas Specialized Chemistry CenterU54HG005031 · NHGRI · UNIVERSITY OF KANSAS LAWRENCE · PI AUBE, JEFFREY · 2008 to 2013
$21.5M
Molecular Approaches To Vaccine Development For Hepatitis CZIADK054503 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$18.9M
Therapy, Vaccine and Model Development in Viral Hepatitis and Liver DiseasesZIADK054505 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$17.5M
Studies of HCV Infection, Vaccine Development and HCV-Host interactionsZIADK054504 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2022
$12.0M
Intramural NIH HHS Z99 DK999999Intramural NIH HHS ZIA DK054503Intramural NIH HHS ZIA DK054504Intramural NIH HHS ZIA DK054505NHGRI NIH HHS U54 HG005031
6 · The paper itself

Abstract

Fluoxazolevir is an aryloxazole-based entry inhibitor of hepatitis C virus (HCV). We show that fluoxazolevir inhibits fusion of HCV with hepatic cells by binding HCV envelope protein 1 to prevent fusion. Nine of ten fluoxazolevir resistance-associated substitutions are in envelope protein 1, and four are in a putative fusion peptide. Pharmacokinetic studies in mice, rats and dogs revealed that fluoxazolevir localizes to the liver. A 4-week intraperitoneal regimen of fluoxazolevir in humanized chimeric mice infected with HCV genotypes 1b, 2a or 3 resulted in a 2-log reduction in viraemia, without evidence of drug resistance. In comparison, daclatasvir, an approved HCV drug, suppressed more than 3 log of viraemia but is associated with the emergence of resistance-associated substitutions in mice. Combination therapy using fluoxazolevir and daclatasvir cleared HCV genotypes 1b and 3 in mice. Fluoxazolevir combined with glecaprevir and pibrentasvir was also effective in clearing multidrug-resistant HCV replication in mice. Fluoxazolevir may be promising as the next generation of combination drug cocktails for HCV treatment.

Indexed as

AnimalsAntiviral AgentsCarbamatesDisease Models, AnimalDogsDrug Therapy, CombinationGenotypeHepacivirusHepatitis CHumansImidazolesMaleMicePyrrolidinesRatsRats, Sprague-DawleyAntiviral AgentsCarbamatesdaclatasvirImidazolesPyrrolidinesValineViral Envelope Proteins

Identifiers

PMID32868923
PMCPMC7677215
OpenAlexW3082476330

What OpenQuestion holds

Textmetadata
LicenceTDM
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.