The γ-lactam nitrogen substituent affects M^pro inhibition.

		aIC50 [μM]
i		8.5 ± 1.4
ii		>100
iii		4.3 ± 0.1
iv		4.7 ± 1.1
v		2.7 ± 0.2
vi		4.4 ± 0.7
vii		1.3 ± 0.1

^aAssays were performed as reported using SPE-MS, employing SARS-CoV-2 M^pro (0.05 μM) and substrate peptide (2.0 μM).⁴² Results are means of two independent runs each composed of technical duplicates (n = 2; mean ± SD). Representative dose response curves of selected γ-lactams are shown in Fig. 2.