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Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376

By Xiaodong Luan, Weijuan Shang, Yifei Wang, Wanchao Yin, Yi Jiang, Siqin Feng, Yiyang Wang, Meixi Liu, Ruilin Zhou, Zhiyu Zhang, Feng Wang, Wang Cheng, Minqi Gao, Hui Wang, Wei Wu, Ran Tian, Zhuang Tian, Ye Jin, Ruotian Jiang, Leike Zhang, H. Eric Xu, Shuyang Zhang

Posted 08 Jun 2020
bioRxiv DOI: 10.1101/2020.06.07.138677

The pandemic of SARS-CoV-2 coronavirus disease-2019 (COVID-19) caused by SARS-COV-2 continues to ravage many countries in the world. Mpro is an indispensable protein for viral translation in SARS-CoV-2 and a potential target in high-specificity anti-SARS-CoV-2 drug screening. In this study, to explore potential drugs for treating COVID-19, we elucidated the structure of SARS-CoV-2 Mpro and explored the interaction between Mpro and GC376, an antiviral drug used to treat a range of coronaviruses in Feline via inhibiting Mpro. The availability and safety of GC376 were proved by biochemical and cell experiments in vitro. We determined the structure of an important protein, Mpro, in SARS-CoV-2, and revealed the interaction of GC376 with the viral substrate and inhibition of the catalytic site of SARS-CoV-2 Mpro. ### Competing Interest Statement The authors have declared no competing interest.

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