SARS-CoV-2-IN-16 (Compound 12) is a potent SARS-CoV-2 nucleocapsid protein ( NPro ) inhibitor. SARS-CoV-2-IN-16 exhibits potent anti-viral activity with the EC 50 of 3.69 μM. SARS-CoV-2-IN-16 binds to NPro with the low K D value of 7.82 μM, suggesting that SARS-CoV-2-IN-16 is a potent NPro ligand.