3.1.2  Substrate‐derived Mpro inhibitors
To date, no approved drugs or vaccines are available for treating a coronavirus infection. In a race to identify chemotherapeutic options, various approaches, such as chemical synthesis, testing of natural products, and virtual screening of compound libraries, have been used. The systematic design of inhibitors of CoV Mpro was essentially based on the enzyme's substrate. In general, a substrate can be transformed into a good inhibitor by modifying part of its sequence such that it binds to the catalytic cysteine in either a reversible or an irreversible manner. Peptide inhibitors are designed by attaching a reactive group (also known as warhead group) to peptides that mimic the natural substrate. The partial peptide substrate sequence for SARS‐CoV‐1 Mpro is mentioned in Figure 10, indicating the specific subsite of each amino acid residue.
Figure 10  A, SARS‐CoV‐1 Mpro partial substrate sequence. B, (Overlay) structures of SARS‐CoV Mpro inhibitors. Mpro, main protease; SARS‐CoV, severe acute respiratory syndrome coronavirus [Color figure can be viewed at wileyonlinelibrary.com]