 The 3CL protease of SARS-CoV-2 is inhibited by PF00835231 in vitro. Here, the authors show that the prodrug PF07304814 has broad spectrum activity, inhibiting SARS-CoV and SARS-CoV-2 in mice and its ADME and safety profile support clinical development. This article was authored by Britain Borers, Rhys M. Jones, Brandon J. Anson, and others.