Figure 5
N-substituent optimization of ebselen leads to nanomolar potent inhibitors. (a,b) General structures of benzisoselenazol-3(2H)-ones 1a–1g (a) and bis(2-carbamoyl)phenyl diselenides 2a, 2d, 2e, 2h (b) used in our study. (c,d) Relative activity of the PLproSARS (black) and PLproCoV2 (grey) in the presence of 20 μM of inhibitors being benzisoselenazolones 1a–1g (c) and diselenides 2a, 2b, 2d and 2e (d). (e,f) Relative activity of the PLproSARS and PLproCoV2 in the presence of 2 μM of inhibitors being benzisoselenazolones 1a–1g (e) and diselenides 2a, 2b, 2d and 2e (f). g, Inhibitory activity for selected ebselen derivatives substituted on the phenyl ring 1d and 1e and related diselenides 2d and 2e (the acyclic forms of 1d and 1e), respectively, toward PLproCoV2.
