Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses
David H. Drewry, Frances Potjewyd, Armin Bayati, Jeffery L. Smith, Rebekah J. Dickmander, Stefanie Howell, Sharon Taft-Benz, Sophia M. Min, Mohammad Anwar Hossain, Mark T. Heise, Peter S. McPherson, Nathaniel J. Moorman, Alison D. Axtman
Abstract
disrupts multiple phases of the lifecycle of β-coronaviruses: viral replication and viral entry. The diverse antiviral roles of PIKfyve have not been previously probed comprehensively in a single study or using the same compound set. Our scaffold is a distinct chemotype that lacks the canonical morpholine hinge-binder of classical lipid kinase inhibitors and has a non-overlapping kinase off-target profile with known PIKfyve inhibitors. Our chemical probe set can be used by the community to further characterize the role of PIKfyve in virology.