LY1 is a potent, selective and covalent inhibitor against both SARS-CoV-2 PL pro and M pro with K d values of 1.5 μM and 2.3 μM for M pro C145A protein and PL pro C111A protein, respectively. LY1 potent against the viral proteases, with IC 50 s of 0.12 μM and 0.99 μM against M pro and PL pro. LY1 shows high selectivity over other kinases, human proteases and metalloenzyme.