Evidence map›Paper›PMID 35526097›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Identification of FDA-approved bifonazole as a SARS-CoV-2 blocking agent following a bioreporter drug screen.

Zaid Taha, Rozanne Arulanandam, Glib Maznyi, Elena Godbout, Madalina E Carter-Timofte, Naziia Kurmasheva, Line S Reinert, Andrew Chen, Mathieu J F Crupi, Stephen Boulton and 23 more

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

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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

33 authors at 4 institutions in 2 countries.

Zaid TahaCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Rozanne ArulanandamCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Glib MaznyiCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Elena GodboutCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Madalina E Carter-TimofteDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Naziia KurmashevaDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Line S ReinertDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Andrew ChenCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Mathieu J F CrupiCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Stephen BoultonCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Geneviève LarocheDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Alexandra PhanDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Reza RezaeiCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Nouf AlluqmaniCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Anna JirovecCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Alexandra AcalCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Emily E F FeketeCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Ragunath SingaraveluCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Julia PetrykCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Manja IdornDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
Kyle G PottsAlberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Hayley TodescoAlberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Cini JohnAlberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Douglas J MahoneyAlberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Carolina S IlkowCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Patrick GiguèreDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Tommy AlainDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada.
Marceline CôtéDepartment of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Søren R PaludanDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
David OlagnierDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
John C BellCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Taha AzadCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Jean-Simon DialloCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: jsdiallo@ohri.ca.
University of Ottawa · CAOttawa Hospital · CAAarhus University · DKUniversity of Calgary · CA

Funding

CIHR INI-147824CIHR OV3 170632
6 · The paper itself

Abstract

We established a split nanoluciferase complementation assay to rapidly screen for inhibitors that interfere with binding of the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein with its target receptor, angiotensin-converting enzyme 2 (ACE2). After a screen of 1,200 US Food and Drug Administration (FDA)-approved compounds, we identified bifonazole, an imidazole-based antifungal agent, as a competitive inhibitor of RBD-ACE2 binding. Mechanistically, bifonazole binds ACE2 around residue K353, which prevents association with the RBD, affecting entry and replication of spike-pseudotyped viruses as well as native SARS-CoV-2 and its variants of concern (VOCs). Intranasal administration of bifonazole reduces lethality in K18-hACE2 mice challenged with vesicular stomatitis virus (VSV)-spike by 40%, with a similar benefit after live SARS-CoV-2 challenge. Our screen identified an antiviral agent that is effective against SARS-CoV-2 and VOCs such as Omicron that employ the same receptor to infect cells and therefore has high potential to be repurposed to control, treat, or prevent coronavirus disease 2019 (COVID-19).

Indexed as

Antiviral AgentsCOVID-19 Drug TreatmentImidazolesSARS-CoV-2Angiotensin-Converting Enzyme 2AnimalsMiceProtein BindingSpike Glycoprotein, CoronavirusUnited StatesUnited States Food and Drug AdministrationAngiotensin-Converting Enzyme 2Antiviral AgentsbifonazoleImidazolesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2bifonazoleCOVID-19drug discoveryhigh-throughput screeningnanoluciferase bioreporterSARS-CoV-2

Identifiers

PMID35526097
PMCPMC9075979
OpenAlexW4229069908

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.