Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor

Journal of Virology
Yi-Ying ChouRaphaël Gaudin

Abstract

Virus entry into cells is a multistep process that often requires the subversion of subcellular machineries. A more complete understanding of these steps is necessary to develop new antiviral strategies. While studying the potential role of the actin network and one of its master regulators, the small GTPase Cdc42, during Junin virus (JUNV) entry, we serendipitously uncovered the small molecule ZCL278, reported to inhibit Cdc42 function as an entry inhibitor for JUNV and for vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus but not for the nonenveloped poliovirus. Although ZCL278 did not interfere with JUNV attachment to the cell surface or virus particle internalization into host cells, it prevented the release of JUNV ribonucleoprotein cores into the cytosol and decreased pH-mediated viral fusion with host membranes. We also identified SVG-A astroglial cell-derived cells to be highly permissive for JUNV infection and generated new cell lines expressing fluorescently tagged Rab5c or Rab7a or lacking Cdc42 using clustered regularly interspaced short palindromic repeat (CRISPR)-caspase 9 (Cas9) gene-editing strategies. Aided by these tools, we uncovered that perturbations in the actin cytoskeleton ...Continue Reading

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Citations

Nov 5, 2016·Molecular Biology of the Cell·François AguetTom Kirchhausen
Feb 1, 2019·Journal of Virology·C E HulsebergJ M White
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Aug 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yuan-Lin KangTom Kirchhausen
Aug 1, 2018·Nature Communications·Marco Padilla-RodriguezGhassan Mouneimne
Jun 16, 2021·Developmental Cell·Yi-Ying ChouTom Kirchhausen
Jul 3, 2021·Viruses·Yu-Jin KimJuan C de la Torre

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