Evidence map›Paper›PMID 38956870›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Discovery of a novel inhibitor of macropinocytosis with antiviral activity.

Bartlomiej Porebski, Wanda Christ, Alba Corman, Martin Haraldsson, Myriam Barz, Louise Lidemalm, Maria Häggblad, Juliana Ilmain, Shane C Wright, Matilde Murga and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

21 authors.

Bartlomiej PorebskiScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Wanda ChristCenter of Infectious Medicine, Department of Medicine, Karolinska Institutet, 141-86 Huddinge, Sweden.
Alba CormanScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Martin HaraldssonChemical Biology Consortium Sweden, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Myriam BarzScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Louise LidemalmScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Maria HäggbladScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Juliana IlmainGrossman School of Medicine, New York University, New York, NY 10016, USA.
Shane C WrightDepartment of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Matilde MurgaGenomic Instability Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Jan SchlegelScience for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Malin JarviusDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden; Chemical Biology Consortium Sweden, Science for Life Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden.
Maris LapinsDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden.
Erdinc SezginScience for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Gira BhabhaGrossman School of Medicine, New York University, New York, NY 10016, USA.
Volker M LauschkeDepartment of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden; Margarete Fischer-Bosch Institute of Clinical Pharmacology, D-70376 Stuttgart, Germany; University of Tuebingen, 72074 Tuebingen, Germany.
Jordi Carreras-PuigvertDepartment of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden; Chemical Biology Consortium Sweden, Science for Life Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden.
Miguel LafargaDepartament of Anatomy and Cellular Biology, Neurodegenerative Diseases Network (CIBERNED), University of Cantabria-IDIVAL, 39011 Santander, Spain.
Jonas KlingströmCenter of Infectious Medicine, Department of Medicine, Karolinska Institutet, 141-86 Huddinge, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden.
Daniela HühnScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
Oscar Fernandez-CapetilloScience for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden; Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain. Electronic address: oscar.fernandez-capetillo@ki.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several viruses hijack various forms of endocytosis in order to infect host cells. Here, we report the discovery of a molecule with antiviral properties that we named virapinib, which limits viral entry by macropinocytosis. The identification of virapinib derives from a chemical screen using high-throughput microscopy, where we identified chemical entities capable of preventing infection with a pseudotype virus expressing the spike (S) protein from SARS-CoV-2. Subsequent experiments confirmed the capacity of virapinib to inhibit infection by SARS-CoV-2, as well as by additional viruses, such as mpox virus and TBEV. Mechanistic analyses revealed that the compound inhibited macropinocytosis, limiting this entry route for the viruses. Importantly, virapinib has no significant toxicity to host cells. In summary, we present the discovery of a molecule that inhibits macropinocytosis, thereby limiting the infectivity of viruses that use this entry route such as SARS-CoV2.

Indexed as

Antiviral AgentsPinocytosisSARS-CoV-2Virus InternalizationAnimalsChlorocebus aethiopsCOVID-19COVID-19 Drug TreatmentDrug DiscoveryHumansSpike Glycoprotein, CoronavirusVero CellsAntiviral AgentsSpike Glycoprotein, Coronavirusantiviralschemical screendrug developmentmacropinocytosismpox viruspseudotype virusSARS-CoV-2tick-borne encephalitis virus

Identifiers

PMID38956870
PMCPMC11403221

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.