Actividad Investigadora
Discovery of a novel inhibitor of macropinocytosis with antiviral activity
Fecha de publicación:
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Autores de IDIVAL
Autores ajenos al IDIVAL
- Porebski, Bartlomiej
- Christ, Wanda
- Corman, Alba
- Haraldsson, Martin
- Barz, Myriam
- Lidemalm, Louise
- Haggblad, Maria
- Ilmain, Juliana
- Wright, Shane C
- Murga, Matilde
- Schlegel, Jan
- Jarvius, Malin
- Lapins, Maris
- Sezgin, Erdinc
- Bhabha, Gira
- Lauschke, Volker M
- Carreras-Puigvert, Jordi
- Klingstrom, Jonas
- Huhn, Daniela
- Fernandez-Capetillo, Oscar
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.
Datos de la publicación
- ISSN/ISSNe:
- 1525-0016, 1525-0024
- Tipo:
- Article
- Páginas:
- 3012-3024
- PubMed:
- 38956870
MOLECULAR THERAPY Cell Press
Citas Recibidas en Web of Science: 2
Documentos
- No hay documentos
Filiaciones
Keywords
- SARS-CoV-2, antivirals, chemical screen, drug development, macropinocytosis, mpox virus, pseudotype virus, tick-borne encephalitis virus
