Discovery of highly potent SARS-CoV-2 M<sup>pro</sup> inhibitors based on benzoisothiazolone scaffold.
Chen W, Feng B, Han S, Wang P, Chen W, Zang Y, Li J, Hu Y.
The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (M<sup>pro</sup>) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 M<sup>pro</sup> inhibition with an IC<sub>50</sub> value of 116 nM and selectivity against SARS-CoV-2 M<sup>pro</sup> when compared to PL<sup>pro</sup> and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.