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dc.contributor.authorWeston, Stuart
dc.contributor.authorBaracco, Lauren
dc.contributor.authorKeller, Chloe
dc.contributor.authorMatthews, Krystal
dc.contributor.authorMcGrath, Marisa E
dc.contributor.authorLogue, James
dc.contributor.authorLiang, Janie
dc.contributor.authorDyall, Julie
dc.contributor.authorHolbrook, Michael R
dc.contributor.authorHensley, Lisa E
dc.contributor.authorJahrling, Peter B
dc.contributor.authorYu, Wenbo
dc.contributor.authorMacKerell, Alexander D
dc.contributor.authorFrieman, Matthew B
dc.date.accessioned2020-12-14T14:42:40Z
dc.date.available2020-12-14T14:42:40Z
dc.date.issued2020-11-12
dc.identifier.urihttp://hdl.handle.net/10713/14255
dc.description.abstractThe SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI complex as a potential host factor for both viruses. In mammalian systems siRNA-mediated knockdown of SKI genes inhibited replication of IAV and MERS-CoV. In silico modeling and database screening identified a binding pocket on the SKI complex and compounds predicted to bind. Experimental assays of those compounds identified three chemical structures that were antiviral against IAV and MERS-CoV along with the filoviruses Ebola and Marburg and two further coronaviruses, SARS-CoV and SARS-CoV-2. The mechanism of antiviral activity is through inhibition of viral RNA production. This work defines the mammalian SKI complex as a broad-spectrum antiviral drug target and identifies lead compounds for further development.en_US
dc.description.urihttps://doi.org/10.1073/pnas.2012939117en_US
dc.language.isoenen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subjectantiviral host factoren_US
dc.subjectbroad-spectrum antiviralen_US
dc.subjectcoronavirusen_US
dc.subjectfilovirusen_US
dc.subjectinfluenzaen_US
dc.titleThe SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.doi10.1073/pnas.2012939117
dc.identifier.pmid33184176
dc.source.volume117
dc.source.issue48
dc.source.beginpage30687
dc.source.endpage30698
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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