F594-1001 (compound 6) hydrochloride is a potent and highly selective SARS-CoV-2 Mac1-ADP-ribose inhibitor with IC 50 s of 8.5 μM, 68 μM and 45 μM for SARS-CoV-2 in AS, FP , and FRET assays, respectively. F594-1001 hydrochloride directly binds to SARS-CoV-2 Mac1 and exhibits a dose-dependent inhibition of Mac1 ADP-ribosylhydrolase activity.