Evidence map›Paper›PMID 35891332›Full record

ArticleViruses2022

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication.

Lucca R Policastro, Isabela Dolci, Andre S Godoy, José V J Silva Júnior, Uriel E A Ruiz, Igor A Santos, Ana C G Jardim, Kirandeep Samby, Jeremy N Burrows, Timothy N C Wells and 3 more

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

Article in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

13 authors at 5 institutions in 2 countries.

Lucca R PolicastroSão Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.ORCID 0000-0001-5584-5391
Isabela DolciSão Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.
Andre S GodoySão Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.ORCID 0000-0002-0613-9164
José V J Silva JúniorVirology Sector, Department of Preventive Veterinary Medicine, Federal University of Santa Maria, Santa Maria 97105-900, Brazil.
Uriel E A RuizInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38405-302, Brazil.
Igor A SantosInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38405-302, Brazil.ORCID 0000-0001-7750-4045
Ana C G JardimInstitute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia 38405-302, Brazil.ORCID 0000-0002-6348-7923
Kirandeep SambyMedicines for Malaria Venture, P.O. Box 1826, 1215 Geneva, Switzerland.
Jeremy N BurrowsMedicines for Malaria Venture, P.O. Box 1826, 1215 Geneva, Switzerland.
Timothy N C WellsMedicines for Malaria Venture, P.O. Box 1826, 1215 Geneva, Switzerland.
Laura H V G GilAggeu Magalhães Institute, IAM-FIOCRUZ, Recife 50670-420, Brazil.
Glaucius OlivaSão Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.ORCID 0000-0003-2719-0302
Rafaela S FernandesSão Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.ORCID 0000-0002-4332-0448
Universidade de São Paulo · BRMedicines for Malaria Venture · CHUniversidade Federal de Uberlândia · BRFundação Oswaldo Cruz · BRUniversidade Federal de Pernambuco · BR

Funding

Bill & Melinda Gates Foundation INV-007155/19-BMGF-006
6 · The paper itself

Abstract

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.

Indexed as

Chikungunya FeverChikungunya virusVirusesAntifungal AgentsAntiviral AgentsHumansItraconazoleLuciferasesRNA, ViralVirus ReplicationAntifungal AgentsAntiviral AgentsItraconazoleLuciferasesnanolucRNA, ViralantiviralChikungunya virusdrug developmentItraconazolereplicon-based assays

Identifiers

PMID35891332
PMCPMC9317443
OpenAlexW4283325065

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.