@article{10902/34119,
year = {2024},
url = {https://hdl.handle.net/10902/34119},
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.},
organization = {ACKNOWLEDGMENTS: The authors acknowledge the support from the Chemical Biology Consortium Sweden (CBCS), node Uppsala university, a national research infrastructure funded by the Swedish Research Council (dr.nr.2021-00179) and SciLifeLab; Dr Lars Haag at the Electron Microscopy Unit, Karolinska Institutet for support with TEM experiments and the Bioinformatics and Expression Analysis facility, Karolinska Institutet, for help with RNA-seq. Research was funded by grants from the Cancerfonden foundation (CAN 21/1529) and the Swedish Research Council (538-2014-31) to O.F.-C.; the Swedish Society for Medical Research (P18-0098; PD20-0153) to S.C.W.; the Swedish Research Council (grant agreement nos. 2019-01837 and 2021-02801) and the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant no. 875510) to V.M.L.; the Swedish Research Council Starting Grant (2020-02682) and Human Frontier Science Program (RGP0025/ 2022) to E.S.; and a Marie Skłodowska-Curie Actions Postdoctoral Fellowship (101059180) and a KI Virus Research Grant to J.S.},
publisher = {Academic Press/Cell Press},
publisher = {Molecular Therapy, 2024, 39(9), 3012-3024},
title = {Discovery of a novel inhibitor of macropinocytosis with antiviral activity},
author = {Porebski, Bartlomiej and Christ, Wanda and Corman, Alba and Haraldsson, Martin and Barz, Myriam and Lidemalm, Louise and Häggblad, Maria and Ilmain, Juliana and Wright, Shane C. and Murga, Matilde and Schlegel, Jan and Jarvius, Malin and Lapins, Maris and Sezgin, Erdinc and Bhabha, Gira and Lauschke, Volker M. and Carreras-Puigvert, Jordi and Lafarga Coscojuela, Miguel Ángel and Klingström, Jonas and Hühn, Daniela},
}