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Simeprevir suppresses SARS-CoV-2 replication and synergizes with remdesivir

biorxiv. 2020-05; 
ProfileHo Sing Lo, Kenrie P. Y. Hui, Hei-Ming Lai, Khadija Shahed Khan, Simranjeet Kaur, Zhongqi Li, Anthony K. N. Chan, Hayley Hei-Yin Cheung, Ka Chun Ng, John Chi Wang Ho, Yu Wai Chen, Bowen Ma, Peter Man-Hin Cheung, Donghyuk Shin, Kaidao Wang, Kuen-Phon Wu, Ivan Dikic, Po-Huang Liang, Zhong Zuo, Francis K. L. Chan, David S. C. Hui, Vincent C. T. Mok, Kam-Bo Wong, Ho Ko, Wei Shen Aik, Michael C. W. Chan, ProfileWai-Lung Ng
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Codon Optimization The sequence of SARS-CoV-2 Mpro was obtained from GenBank (accession number: YP_009725301), codon-optimized, and ordered from GenScript Get A Quote

摘要

The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a global threat to human health. By in vitro screening and biochemical characterization, we identified the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. We also revealed that simeprevir synergizes with the RNA-dependent RNA polymerase (RdRP) inhibitor remdesivir to suppress the replication of SARS-CoV-2 in vitro. Our results provide preclinical rationale for the combination treatment of simeprevir and remdesivir for the pharmacological management of COVID-19 patients.

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