Evidence map›Paper›PMID 22535622›Full record

ArticleThe Journal of antimicrobial chemotherapy2012

Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug.

Eloise Mastrangelo, Margherita Pezzullo, Tine De Burghgraeve, Suzanne Kaptein, Boris Pastorino, Kai Dallmeier, Xavier de Lamballerie, Johan Neyts, Alicia M Hanson, David N Frick and 2 more

2 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 198 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 5 pooled it
11.9field-weighted citation impact, top 1% 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.

NCT04551755 phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

The Safety and Efficacy Outcome of Ivermectin Plus Doxycycline in Treatment of RT-PCR Positive Adult Mild Covid-19 Cases: a Randomized Double Blind Placebo Controlled Trial

TypeinterventionalSponsorBangladesh Medical Research Council (BMRC)Ran2020 to 2020Enrolled188ConditionsCovid19ArmsIvermectin and Doxycycline, Placebo
NCT04595136 phase1 / phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

A Two-arm Randomized Double-blind Study With COVID19-0001-USR Administered Via Nebulization to Patients With Mild and/or Moderate Severe Acute Respiratory Syndrome (SARS-COV-2) Infection to Decrease Viral Load

TypeinterventionalSponsorUnited Medical SpecialtiesRan2020 to 2021Enrolled60ConditionsSARS-CoV-2 InfectionArmsDrug COVID19-0001-USR, normal saline
3 · Its place in the literature

Who cites it

198 citing papers in PubMed, 5 syntheses or guidelines pooled it, 421 citations in OpenAlex.

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  8. Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy · 2021
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  17. Ivermectin repurposing for COVID-19: pharmacological and bibliometric analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2025
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138 more citing papers are in PubMed but not listed here.

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

12 authors at 5 institutions in 4 countries.

Eloise MastrangeloDipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, via Celoria 26, 20133 Milano, Italy.
Margherita Pezzullo
Tine De Burghgraeve
Suzanne Kaptein
Boris Pastorino
Kai Dallmeier
Xavier de Lamballerie
Johan Neyts
Alicia M Hanson
David N Frick
Martino Bolognesi
Mario Milani
KU Leuven · BEUniversity of Milan · ITUniversity of Wisconsin–Milwaukee · USInstituto Biofisika · ESRega Institute for Medical Research · BE

Funding

Antiviral potential of helicase inhibitorsR01AI088001 · NIAID · UNIVERSITY OF WISCONSIN MILWAUKEE · PI FRICK, DAVID N · 2010 to 2012
$1.1M
NIAID NIH HHS R01 AI088001
6 · The paper itself

Abstract

objectivesInfection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed.

methodsStarting from the crystal structure of the NS3 helicase from Kunjin virus (an Australian variant of West Nile virus), we identified a novel, unexploited protein site that might be involved in the helicase catalytic cycle and could thus in principle be targeted for enzyme inhibition. In silico docking of a library of small molecules allowed us to identify a few selected compounds with high predicted affinity for the new site. Their activity against helicases from several flaviviruses was confirmed in in vitro helicase/enzymatic assays. The effect on the in vitro replication of flaviviruses was then evaluated.

resultsIvermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication (EC₅₀ values in the sub-nanomolar range). Moreover, ivermectin inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalitis viruses. Ivermectin exerts its effect at a timepoint that coincides with the onset of intracellular viral RNA synthesis, as expected for a molecule that specifically targets the viral helicase.

conclusionsThe well-tolerated drug ivermectin may hold great potential for treatment of YFV infections. Furthermore, structure-based optimization may result in analogues exerting potent activity against flaviviruses other than YFV.

Indexed as

AnimalsAntiviral AgentsChlorocebus aethiopsDEAD-box RNA HelicasesDengue VirusEncephalitis Viruses, JapaneseEncephalitis Viruses, Tick-BorneEnzyme InhibitorsIvermectinMolecular Dynamics SimulationNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesVero CellsViral Nonstructural ProteinsViral ProteasesAntiviral AgentsDEAD-box RNA HelicasesEnzyme InhibitorsIvermectinNS3 protein, flavivirusNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsViral Proteases

Identifiers

PMID22535622
PMCPMC3888155
OpenAlexW2165157662

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.