Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

作     者：Haoran Peng Cuiling Ding Liangliang Jiang Wanda Tang Yan Liu Lanjuan Zhao Zhigang Yi Hao Ren Chong Li Yanhua He Xu Zheng Hailin Tang Zhihui Chen Zhongtian Qi Ping Zhao Haoran Peng;Cuiling Ding;Liangliang Jiang;Wanda Tang;Yan Liu;Lanjuan Zhao;Zhigang Yi;Hao Ren;Chong Li;Yanhua He;Xu Zheng;Hailin Tang;Zhihui Chen;Zhongtian Qi;Ping Zhao

作者机构：Department of MicrobiologySecond Military Medical UniversityShanghai Key Laboratory of Medical BiodefenseShanghai 200433China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS)School of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China Cancer InstituteFudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Infectious DiseaseChanghai HospitalShanghai 200433China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2022年第65卷第6期

页      面：1181-1197页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(31570170) the National Key Research and Development Program of China(2016YFC1200401) 

主　　题：SARS-CoV-2 drug repurposing drug screening hamster model D614G variant drug resistance 

摘      要：The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global *** candidates with high efficacy,ready availability,and that do not develop resistance are in urgent *** that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in *** this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule *** them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human *** compounds disturb multiple processes of the SARSCoV-2 life *** prophylactic efficacies were determined in vivo using Syrian hamsters challenged with *** compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G *** for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d *** particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.