Evidence map›Paper›PMID 32764799›Full record

ArticlePloS one2020

Structurally distinct cyclosporin and sanglifehrin analogs CRV431 and NV556 suppress established HCV infection in humanized-liver mice.

Michael Bobardt, Magnus Joakim Hansson, Patrick Mayo, Daren Ure, Robert Foster, Philippe Gallay

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Non-Immunosuppressive Cyclophilin Inhibitors.Angewandte Chemie (International ed. in English) · 2022
    Review
  7. Review
  8. Review
  9. Article
  10. Review
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

6 authors at 3 institutions in 2 countries.

Michael BobardtDepartment of Immunology & Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.
Magnus Joakim HanssonNeuroVive Pharmaceutical AB, Lund, Sweden.
Patrick MayoHepion Pharmaceuticals, Edison, New Jersey, United States of America.
Daren UreHepion Pharmaceuticals, Edison, New Jersey, United States of America.
Robert FosterHepion Pharmaceuticals, Edison, New Jersey, United States of America.
Philippe GallayDepartment of Immunology & Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.ORCID 0000-0002-6151-4764
Edison Pharmaceuticals (United States) · USScripps Research Institute · USNeuroVive Pharmaceutical (Sweden) · SE

Funding

Analyses of the Antiviral and Antifibrotic Mechanisms of Action of NS5A and Cyclophilin InhibitorsR01AI125365 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI GALLAY, PHILIPPE ANDRE · 2017 to 2021
$2.4M
Non-immunosuppressive Sanglifehrin Analogs as Therapeutic Agents for Viral Hepatitis-induced Liver Damage DevelopmentR01AI143931 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI GALLAY, PHILIPPE ANDRE · 2020 to 2024
$2.2M
NIAID NIH HHS R01 AI125365NIAID NIH HHS R01 AI143931
6 · The paper itself

Abstract

We previously reported that the non-immunosuppressive cyclophilin inhibitors (CypIs)-cyclosporin A analog CRV431 and sanglifehrin analog NV556-efficiently inhibit HCV replication in vitro. In this study, we asked whether they can also reduce HCV replication in vivo. We found that a single oral administration of CRV431 and NV556 to HCV-infected humanized-liver mice drastically reduced HCV blood levels. The antiviral effect was observed when CRV431 or NV556 were each individually administered with HCV, 3, 6 weeks or even 3 months post-infection when viral replication is robust. These results were confirmed in chimeric mice implanted with human hepatocytes isolated from three distinct donors. Remarkably, no viral rebound was observed 5 months after a single dose administration of 50 mg/kg of CRV431 or NV556 four weeks post-HCV infection, indicating the possibility of suppression of an established viral infection. Since we recently demonstrated that both CRV431 and NV556 also inhibit the development of liver fibrosis and hepatocellular carcinoma in nonviral-induced non-alcoholic steatohepatitis mouse models, our present data suggest that the two entirely structurally different CypIs-CRV431 and NV556-derived from unrelated natural products, represent attractive partners to current direct-acting agent (DAA) regimens for the treatment of hepatitis C and liver diseases.

Indexed as

AnimalsAntiviral AgentsCyclosporinsHepacivirusHepatitis CHumansLiverMiceMice, SCIDMice, TransgenicVirus ReplicationAntiviral AgentsCRV-431Cyclosporins

Identifiers

PMID32764799
PMCPMC7413547
OpenAlexW3048014675

What OpenQuestion holds

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LicenceCC BY
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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.