Bartlomiej Porebski, Wanda Christ, Alba Corman, Martin Haraldsson, Myriam Barz, Louise Lidemalm, Maria Häggblad, Juliana Ilmain, Shane C Wright, Matilde Murga, Jan Schlegel, Malin Jarvius, Maris Lapins, Erdinc Sezgin, Gira Bhabha, Volker M Lauschke, Jordi Carreras-Puigvert, Miguel Lafarga, Jonas Klingström, Daniela Hühn, Oscar Fernandez-Capetillo
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Discovery of a novel inhibitor of macropinocytosis with antiviral activity.
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.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.