Fig. 5: Characterization of a designed covalent PLpro inhibitor, compound 7.
From: Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2
a Fluorogenic peptide activity assay after 30-min preincubation with compound 7. Data are plotted for each of n = 2 independent samples. IC50 is the concentration at which 50% inhibition was observed. Curve is the nonlinear regression to the normalized inhibitor dose response equation. b Time-dependent characterization with a fluorogenic peptide assay. Data points are kobs values determined by fitting the exponential decay equation to initial rates determined at various inhibitor concentrations and preincubation times, normalized to no preincubation. kobs data are presented as mean values determined from n = 2 independent samples. Line represents the linear regression yielding as its slope the second-order rate constant (kinact/KI). c Intact protein ESI-MS spectra of PLpro (black) and PLpro incubated with 7 (red); a.i., arbitrary intensity; m/z, mass-to-charge ratio. d Percent viability of Vero E6 cells after 48 h following pretreatment with 7 (black squares), pretreatment with 7 and infection with SARS-CoV-2 (red circles), or pretreatment with remdesivir and infected with SARS-CoV-2 (blue triangles). Data are plotted as the mean of n = 2 independent samples. EC50 is the concentration at which 50% effect was observed. Curves are nonlinear regressions to the normalized dose response equation. Source data are provided as a Source Data file.
