Crystallization. Crystallization of Mpro in complex with compounds, was carried out as previously described . Briefly, Mpro, stored in 20 mM Tris-HCl, 150 mM NaCl, 1 mM EDTA, pH 7.8, 1 mM DTT was incubated at 5 mg/ml (150 μM) with compounds (X77/MG-132) at either 75 µM or 150 µM final concentrations. For X77 also a 500 µM concentration was used. Crystallization experiments were set up after 1h of incubation at RT, by seeding in sitting drops using the Morpheus® kit (Molecular Dimensions) with a Mosquito robot (STPlabtech Ltd., Melbourn Hertfordshire, UK). Crystals appeared within a couple of days, and were flash frozen in liquid nitrogen after a few days of growth. For S-X77 a 5 mM concentration of molecule was needed. For the "old" crystals, crystallization was carried out as described, with 5 mM MG-132 or X77 respectively and crystals were flashfrozen in liquid nitrogen after at least 2 months from their first appearance.