X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases

…, SC Baker, SD Larsen, AD Mesecar

Index: Baez-Santos, Yahira M.; Barraza, Scott J.; Wilson, Michael W.; Agius, Michael P.; Mielech, Anna M.; Davis, Nicole M.; Baker, Susan C.; Larsen, Scott D.; Mesecar, Andrew D. Journal of Medicinal Chemistry, 2014 , vol. 57, # 6 p. 2393 - 2412

Full Text: HTML

Citation Number: 21

Abstract

Structure-guided design was used to generate a series of noncovalent inhibitors with nanomolar potency against the papain-like protease (PLpro) from the SARS coronavirus (CoV). A number of inhibitors exhibit antiviral activity against SARS-CoV infected Vero E6 cells and broadened specificity toward the homologous PLP2 enzyme from the human coronavirus NL63. Selectivity and cytotoxicity studies established a more than 100-fold ...