Molecules, Vol. 28, Pages 3020: Development of FRET and Stress Granule Dual-Based System to Screen for Viral 3C Protease Inhibitors

Molecules, Vol. 28, Pages 3020: Development of FRET and Stress Granule Dual-Based System to Screen for Viral 3C Protease Inhibitors Molecules doi: 10.3390/molecules28073020 Authors: Jingjing Zhang Yingpei Jiang Chunxiu Wu Dan Zhou Jufang Gong Tiejun Zhao Zhigang Jin 3C proteases (3Cpros) of picornaviruses and 3C-like proteases (3CLpros) of coronaviruses and caliciviruses represent a group of structurally and functionally related viral proteases that play pleiotropic roles in supporting the viral life cycle and subverting host antiviral responses. The design and screening for 3C/3CLpro inhibitors may contribute to the development broad-spectrum antiviral therapeutics against viral diseases related to these three families. However, current screening strategies cannot simultaneously assess a compound’s cytotoxicity and its impact on enzymatic activity and protease-mediated physiological processes. The viral induction of stress granules (SGs) in host cells acts as an important antiviral stress response by blocking viral translation and stimulating the host immune response. Most of these viruses have evolved 3C/3CLpro-mediated cleavage of SG core protein G3BP1 to counteract SG formation and disrupt the host defense. Yet, there are no SG-based strategies screening for 3C/3CLpro inhibitors. Here, we developed a fluorescence resonance energy transfer (FRET) and SG dual-based system to screen for 3C/3CLpro inhibitors in living cells. We took advantage...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research