UAWJ9-36-1 is a SARS-CoV-2 Protease inhibitor (IC50 = 51 nM). UAWJ9-36-1 showed potent binding and enzymatic inhibition against the Mpro's from SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1. UAWJ9-36-1 is a promising candidate to be further developed as a broad-spectrum coronavirus antiviral.