The Development of Coronavirus 3C-Like Protease (3CLpro) Inhibitors from 2010 to 2020

Abstract

3CLpro is a key enzyme for the maturation of all coronaviruses and has hence been recognized as a potent drug target for the treatment of coronavirus infection. The present review focuses on the status of various efficacious anti-coronavirus small-molecule inhibitors found from various sources in the past 10 years (2010-2020) and describes in detail the structural characteristics, binding modes and SARs of these 3CLpro inhibitors. To solve the shortcomings of “off-target” side effects and weak inhibitory activity of existing 3CLpro inhibitors, the authors propose a new idea for drug design, combining the emerging PROTAC technology with existing 3CLpro inhibitors. 3CLpro PROTAC degraders are proposed as the next generation of anti-coronavirus drugs.