Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus fusion
JournalJournal of Virology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractThe highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro. Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro. These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses.
SponsorsThis work, including the efforts of Matthew B. Frieman, was funded by HHS|NIH| National Institute of Allergy and Infectious Diseases (NIAID) (AI095569). This work, including the efforts of Judith Miriam White, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (R21AI103601 and R01AI114776). This work, including the efforts of Jeanne M. Sisk, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI118303).
KeywordAbelson tyrosine-protein kinase 2
Middle East Respiratory Syndrome Coronavirus
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84990252098&doi=10.1128%2fJVI.01429-16&partnerID=40&md5=7ae855957d02226d0817b58ee7da918a; http://hdl.handle.net/10713/12403