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• W2274420433 abstract "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 or Cdc42 activity minimally affect JUNV entry, suggesting that the inhibitory effect of ZCL278 is not mediated by ZCL278 interfering with the activity of Cdc42. Instead, ZCL278 appears to redistribute viral particles from endosomal to lysosomal compartments. ZCL278 also inhibited JUNV replication in a mouse model, and no toxicity was detected. Together, our data suggest the unexpected antiviral activity of ZCL278 and highlight its potential for use in the development of valuable new tools to study the intracellular trafficking of pathogens. IMPORTANCE The Junin virus is responsible for outbreaks of Argentine hemorrhagic fever in South America, where 5 million people are at risk. Limited options are currently available to treat infections by Junin virus or other viruses of the Arenaviridae , making the identification of additional tools, including small-molecule inhibitors, of great importance. How Junin virus enters cells is not yet fully understood. Here we describe new cell culture models in which the cells are susceptible to Junin virus infection and to which we applied CRISPR-Cas9 genome engineering strategies to help characterize early steps during virus entry. We also uncovered ZCL278 to be a new antiviral small molecule that potently inhibits the cellular entry of the Junin virus and other enveloped viruses. Moreover, we show that ZCL278 also functions in vivo , thereby preventing Junin virus replication in a mouse model, opening the possibility for the discovery of ZCL278 derivatives of therapeutic potential." @default.
• W2274420433 created "2016-06-24" @default.
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• W2274420433 date "2016-05-01" @default.
• W2274420433 modified "2023-10-13" @default.
• W2274420433 title "Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor" @default.
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• W2274420433 cites W1526128150 @default.
• W2274420433 cites W1532805138 @default.
• W2274420433 cites W1566432282 @default.
• W2274420433 cites W1606338704 @default.
• W2274420433 cites W1973260880 @default.
• W2274420433 cites W1977709885 @default.
• W2274420433 cites W1977944577 @default.
• W2274420433 cites W1978377488 @default.
• W2274420433 cites W1978691529 @default.
• W2274420433 cites W1984834692 @default.
• W2274420433 cites W1992053143 @default.
• W2274420433 cites W2004143097 @default.
• W2274420433 cites W2008110867 @default.
• W2274420433 cites W2009101679 @default.
• W2274420433 cites W2009458372 @default.
• W2274420433 cites W2021039582 @default.
• W2274420433 cites W2021220588 @default.
• W2274420433 cites W2021562772 @default.
• W2274420433 cites W2024399818 @default.
• W2274420433 cites W2044111208 @default.
• W2274420433 cites W2047189878 @default.
• W2274420433 cites W2048296059 @default.
• W2274420433 cites W2053207268 @default.
• W2274420433 cites W2074205741 @default.
• W2274420433 cites W2074750922 @default.
• W2274420433 cites W2075090444 @default.
• W2274420433 cites W2083087851 @default.
• W2274420433 cites W2085075383 @default.
• W2274420433 cites W2085910865 @default.
• W2274420433 cites W2092986345 @default.
• W2274420433 cites W2097170794 @default.
• W2274420433 cites W2098136597 @default.
• W2274420433 cites W2098220852 @default.
• W2274420433 cites W2098912234 @default.
• W2274420433 cites W2099051954 @default.
• W2274420433 cites W2102627055 @default.
• W2274420433 cites W2110084716 @default.
• W2274420433 cites W2112032807 @default.
• W2274420433 cites W2123555845 @default.
• W2274420433 cites W2124335390 @default.
• W2274420433 cites W2124454170 @default.
• W2274420433 cites W2127938800 @default.
• W2274420433 cites W2129393642 @default.
• W2274420433 cites W2130276289 @default.
• W2274420433 cites W2130394030 @default.
• W2274420433 cites W2133150766 @default.
• W2274420433 cites W2134664573 @default.
• W2274420433 cites W2139756641 @default.
• W2274420433 cites W2140928217 @default.
• W2274420433 cites W2146279918 @default.
• W2274420433 cites W2146623463 @default.
• W2274420433 cites W2148440555 @default.
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• W2274420433 doi "https://doi.org/10.1128/jvi.00103-16" @default.
• W2274420433 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4836360" @default.
• W2274420433 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26912630" @default.
• W2274420433 hasPublicationYear "2016" @default.
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