The scaffold of all designed inhibitors was composed of a Leu-Phe dipeptide portion. In most cases, leucine was placed at P2 and phenylalanine at P1. In contrast, in compounds 6 and 7, a nitrile moiety derived from 1-aminocyclopropane-1carboxylic acid (ACC) and glycine, respectively, was added C-terminally from the Leu-Phe portion, shifting it to the P3-P2 position. A variety of well-known warheads was incorporated, most of which were susceptible to the nucleophilic addition of the active site cysteine residues of the proteases. We equipped compounds 6, 7, and 11a-h with a nitrile warhead, 9a-c with an aldehyde, and 12a-b, 13a-b, and 14a-b with a Michael acceptor. The extended α,β-unsaturated moiety in 12-14 might be engaged in interacting with the S1' pocket of the target cysteine proteases. Peptides 5b and 5i possess a cleavable warhead structure. Their design was geared to the structure of 5halopyridin-3-yl 1H-indole-carboxylates, whose indole unit was replaced by the peptide core present in 5b and 5i. Mainly, two N-terminal groups were introduced, i.e., the 1H-indole-2carbonyl and the cinnamoyl group. The indole capping group has already been incorporated into efficient peptidic inhibitors of the main protease of coronaviruses. Initially, we paid attention to the inhibition of our primary targets, i.e., CatL and SARS-CoV-2 M pro . In compound 5b, the Leu-Phe dipeptide portion was combined with the indole capping group and equipped with a 5-chloropyridin-3-yl ester at the C-terminus. Inhibition of both target proteases was observed, however, with Ki values only in the single-digit micromolar range. Both tripeptide nitriles 6 and 7 were active against CatL, but failed to inhibit M pro .