Evidence map›Paper›PMID 24841269›Full record

ArticleAntimicrobial agents and chemotherapy2014

Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.

Adriaan H de Wilde, Dirk Jochmans, Clara C Posthuma, Jessika C Zevenhoven-Dobbe, Stefan van Nieuwkoop, Theo M Bestebroer, Bernadette G van den Hoogen, Johan Neyts, Eric J Snijder

3 registry-linked trialsOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 416 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
416citing papers in PubMed, 4 pooled it
13.7field-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.

NCT04353037 phase2terminatednot on this mapstarted 2020, after this paper: background citation

PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) A Double-blind Placebo Controlled Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19

TypeinterventionalSponsorUnitedHealth GroupRan2020 to 2020Enrolled39ConditionsCoronavirus, Corona Virus InfectionArmsGroup 1 HCQ, Group 2 Placebo
NCT04366739 phase3withdrawnnot on this mapstarted 2020, after this paper: background citation

Repurposing of Chlorpromazine in Covid-19 Treatment

TypeinterventionalSponsorCentre Hospitalier St AnneRan2020 to 2020Enrolled0ConditionsCOVID-19ArmsCHLORPROMAZINE (CPZ), Standard of Care (SOC)
NCT04372628 phase2completednot on this mapstarted 2020, after this paper: background citation

Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19

TypeinterventionalSponsorVanderbilt University Medical CenterRan2020 to 2022Enrolled452ConditionsCOVID-19ArmsLopinavir/Ritonavir 400 mg/100 mg, Placebo
3 · Its place in the literature

Who cites it

416 citing papers in PubMed, 4 syntheses or guidelines pooled it, 747 citations in OpenAlex.

  1. Pooled it
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  7. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2021
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  13. From treating UTI to agranulocytosis.Journal of family medicine and primary care · 2025
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356 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

9 authors at 2 institutions in 2 countries.

Adriaan H de WildeMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
Dirk JochmansRega Institute for Medical Research, KU, Leuven, Belgium.
Clara C PosthumaMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
Jessika C Zevenhoven-DobbeMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
Stefan van NieuwkoopDepartment of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands.
Theo M BestebroerDepartment of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands.
Bernadette G van den HoogenDepartment of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands.
Johan NeytsRega Institute for Medical Research, KU, Leuven, Belgium Johan.Neyts@rega.kuleuven.be E.J.Snijder@LUMC.nl.
Eric J SnijderMolecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands Johan.Neyts@rega.kuleuven.be E.J.Snijder@LUMC.nl.
Leiden University Medical Center · NLRega Institute for Medical Research · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ∼ 30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response.

Indexed as

AnimalsAntiviral AgentsCell LineChlorocebus aethiopsChloroquineChlorpromazineCoronavirus 229E, HumanDrug ApprovalHepatocytesHigh-Throughput Screening AssaysHumansInhibitory Concentration 50LoperamideLopinavirMiddle East Respiratory Syndrome CoronavirusSevere acute respiratory syndrome-related coronavirusAntiviral AgentsChloroquineChlorpromazineLoperamideLopinavirSmall Molecule Libraries

Identifiers

PMID24841269
PMCPMC4136071
OpenAlexW2139603860

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.