Evidence map›Paper›PMID 39861906›Full record

ArticleViruses2025

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Chukwudi A Ofodile, Ikemefuna C Uzochukwu, Fortunatus C Ezebuo, InnocentMary Ejiofor, Mercy Adebola, Innocent Okpoli, Beatrice Cubitt, Haydar Witwit, Chetachi B Okwuanaso, Ngozi Onyemelukwe and 1 more

Abstract read
In one paragraph

Article in Viruses, 2025. 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
–field-weighted citation impact
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.

  1. Review
  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

11 authors.

Chukwudi A OfodileDepartment of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.ORCID 0000-0003-0664-9698
Ikemefuna C UzochukwuDepartment of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.ORCID 0000-0002-5139-1537
Fortunatus C EzebuoDepartment of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.ORCID 0000-0002-2832-1215
InnocentMary EjioforDepartment of Pharmacognosy & Traditional Medicine, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.
Mercy AdebolaDepartment of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.
Innocent OkpoliDepartment of Pharmaceutical & Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.
Beatrice CubittDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8048-410X
Haydar WitwitDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-0174-8454
Chetachi B OkwuanasoDepartment of Medical Laboratory Science, Faculty of Health Sciences and Technology, Nnamdi Azikiwe University, Awka 420218, Anambra, Nigeria.
Ngozi OnyemelukweDepartment of Medical Laboratory Sciences, Faculty of Health Sciences and Technology, University of Nigeria, Nsukka 401105, Enugu, Nigeria.
Juan Carlos de la TorreDepartment of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8171-8115

Funding

A Virus-Free Cell Platform To Discover Inhibitors Of Lassa Fever VirusR01AI125626 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 2017 to 2019
$1.3M
Modulation of Lassa Virus vRNP Activity By Host Cell FactorsR21AI128556 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 2017 to 2018
$554k
NIAID NIH HHS R01 AI125626NIAID NIH HHS R21 AI128556NIH/NIAID AI125626NIH/NIAID AI128556TETFUND/NRF TETFund/DR&D/CE/NRF/STI/24/Vol1
6 · The paper itself

Abstract

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome. Validation of docking protocols were achieved with reference inhibitors of the respective targets. Our in silico docking screen identified five drugs (dexamethasone, tadalafil, mefloquine, ergocalciferol, and flunarizine) with strong predicted binding affinity to LASV proteins involved in the formation of the vRNP. We used cell-based functional assays to evaluate the antiviral activity of the five selected drugs. We found that flunarizine, a calcium-entry blocker, inhibited the vRNP activity of LASV and LCMV and virus surface glycoprotein fusion activity required for mammarenavirus cell entry. Consistently with these findings, flunarizine significantly reduced peak titers of LCMV in a multi-step growth kinetics assay in human A549 cells. Flunarizine is being used in several countries worldwide to treat vertigo and migraine, supporting the interest in exploring its repurposing as a candidate drug to treat LASV infections.

Indexed as

Antiviral AgentsDrug RepositioningFlunarizineLassa virusAnimalsCell LineChlorocebus aethiopsHumansLassa FeverMolecular Docking SimulationViral ProteinsVirus ReplicationAntiviral AgentsFlunarizineViral Proteinsantiviralflunarizinein silico dockingLassa virusLCMVminigenome

Identifiers

PMID39861906
PMCPMC11768584

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.