MPI8 (TG0205221) is an inhibitor of the major protease of SARS-CoV-2 ( MPro ) with high antiviral activity. MPI8 exerts its antiviral effect by dual and selective inhibition of SARS-CoV-2 MPro and host cell cysteine protease L ( cathepsin L ). This dual inhibition enhanced the overall antiviral potency and effect of MPI8. MPI8 can be used in clinical studies of COVID-19.