Comparative Antiviral Efficacy of Viral Protease Inhibitors against the Novel SARS-CoV-2 In Vitro

作     者：Leike Zhang Jia Liu Ruiyuan Cao Mingyue Xu Yan Wu Weijuan Shang Xi Wang Huanyu Zhang Xiaming Jiang Yuan Sun Hengrui Hu Yufeng Li Gang Zou Min Zhang Lei Zhao Wei Li Xiaojia Guo Xiaomei Zhuang Xing-Lou Yang Zheng-Li Shi Fei Deng Zhihong Hu Gengfu Xiao Manli Wang Wu Zhong Leike Zhang;Jia Liu;Ruiyuan Cao;Mingyue Xu;Yan Wu;Weijuan Shang;Xi Wang;Huanyu Zhang;Xiaming Jiang;Yuan Sun;Hengrui Hu;Yufeng Li;Gang Zou;Min Zhang;Lei Zhao;Wei Li;Xiaojia Guo;Xiaomei Zhuang;Xing-Lou Yang;Zheng-Li Shi;Fei Deng;Zhihong Hu;Gengfu Xiao;Manli Wang;Wu Zhong

作者机构：State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China National Engineering Research Center for the Emergency DrugBeijing Institute of Pharmacology and ToxicologyBeijing 100850China CAS Key Laboratory of Molecular Virology and ImmunologyInstitute Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2020年第35卷第6期

页      面：776-784页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported in part by grants from the National Science and Technology Major Projects(Grant Number 2018ZX09711003) National Key Research and Development Project(2020YFC0841700) the National Natural Science Foundation of China(Grant Number 31621061) the Hubei Science and Technology Project(Grant Number 2020FCA003) 

主　　题：Respiratory pharmacology COVID-19 SARS-CoV-2 Protease inhibitor 

摘      要：The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public *** safe and effective antivirals is of urgent demand to cure the huge number of *** proteases are considered potential drug *** human immunodeficiency virus protease inhibitors(lopinavir/ritonavir)has been recommended in the global Solidarity Trial in March launched by World Health ***,there is currently no experimental evidence to support or against its clinical *** evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro,and discussed the possible inhibitory mechanism in *** in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in *** the four tested compounds,lopinavir showed the best inhibitory effect against the novel coronavirus ***,further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen[marketed as Kaletraò,contained lopinavir/ritonavir(200 mg/50 mg)tablets,recommended dosage is 400 mg/10 mg(2 tablets)twice daily].This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma ***,the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.