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Other notable examples of reversible inhibitors are crystal structures of the first clinically approved proteasome inhibitor bortezomib (PS-341) [139] covalently bound to Thr1 of yeast 20S proteasome through the boronic acid moiety (PDB: 2F16) [51], COVID-19 drug nirmatrelvir (PF-07321332) forming a reversible covalent thioimidate adduct with catalytic cysteine Cys145 of SARS-CoV-2 M pro protease in crystals formed by co-crystallization (PDB: 7RFW) or by soaking the apo crystal (PDB: 7RFS) [47], and the structure-based design of reversible covalent BTK inhibitors with tunable residence times [55]

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Folic acid and vitamin B12 work closely together in the body, and some patients may need both