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

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, Hualiang Jiang, Leike Zhang, View ORCID ProfileH. Eric Xu, View ORCID ProfileShuyang Zhang
doi: https://doi.org/10.1101/2020.06.07.138677
Xiaodong Luan
1School of Medicine, Tsinghua University, Haidian District, Beijing, China
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
3Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
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Weijuan Shang
4State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
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Yifei Wang
1School of Medicine, Tsinghua University, Haidian District, Beijing, China
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Wanchao Yin
5The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Yi Jiang
5The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Siqin Feng
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Yiyang Wang
1School of Medicine, Tsinghua University, Haidian District, Beijing, China
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Meixi Liu
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ruilin Zhou
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Zhiyu Zhang
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Feng Wang
6Wuxi Biortus Biosciences Co. Ltd., 6 Dongsheng West Road, Jiangyin 214437, China
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Wang Cheng
6Wuxi Biortus Biosciences Co. Ltd., 6 Dongsheng West Road, Jiangyin 214437, China
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Minqi Gao
6Wuxi Biortus Biosciences Co. Ltd., 6 Dongsheng West Road, Jiangyin 214437, China
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Hui Wang
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Wei Wu
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ran Tian
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Zhuang Tian
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ye Jin
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Hualiang Jiang
5The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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Leike Zhang
4State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
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  • For correspondence: shuyangzhang103@nrdrs.org eric.xu@simm.ac.cn zhangleike@wh.iov.cn
H. Eric Xu
5The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
7University of Chinese Academy of Sciences, Beijing 100049, China
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  • ORCID record for H. Eric Xu
  • For correspondence: shuyangzhang103@nrdrs.org eric.xu@simm.ac.cn zhangleike@wh.iov.cn
Shuyang Zhang
2Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
1School of Medicine, Tsinghua University, Haidian District, Beijing, China
3Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
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  • ORCID record for Shuyang Zhang
  • For correspondence: shuyangzhang103@nrdrs.org eric.xu@simm.ac.cn zhangleike@wh.iov.cn
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Abstract

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 08, 2020.
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Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376
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, Hualiang Jiang, Leike Zhang, H. Eric Xu, Shuyang Zhang
bioRxiv 2020.06.07.138677; doi: https://doi.org/10.1101/2020.06.07.138677
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Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376
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, Hualiang Jiang, Leike Zhang, H. Eric Xu, Shuyang Zhang
bioRxiv 2020.06.07.138677; doi: https://doi.org/10.1101/2020.06.07.138677

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