Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2  

作　　者：Zhijian Xu Danrong Shi Jian-Bao Han Yun Ling Xiangrui Jiang Xiangyun Lu Chuan Li Likun Gong Guangbo Ge Yani Zhang Yi Zang Tian-Zhang Song Xiao-Li Feng Ren-Rong Tian Jia Ji Miaojin Zhu Nanping Wu Chunhui Wu Zhen Wang Yechun Xu Cheng Peng Min Zheng Junling Yang Feifei Du Junliang Wu Peipei Wang Jingshan Shen Jianliang Zhang Yong-Tang Zheng Hangping Yao Weiliang Zhu 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [2]Drug Discovery and Design Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]School of Pharmacy,University of Chinese Academy of Sciences,Beijing,100049,China [4]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310003,China [5]Kunming National High-level Biosafety Research Center for Non-human Primates,Center for Biosafety Mega-Science,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,650107,China [6]Department of Infectious Disease,Shanghai Public Health Clinical Center,Fudan University,Shanghai,201508,China [7]Center for Drug Safety Evaluation and Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [8]Shanghai Frontiers Science Center of TCM Chemical Biology,Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [9]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,650223,China [10]Jinan Microecological Biomedicine Shandong Laboratory,Jinan,250117,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第5期2384-2391,共8页信号转导与靶向治疗（英文）

基　　金：supported by the Natural Science Foundation of Shanghai (21ZR1475600);Science and Technology Commission of Shanghai Municipality (20431900100);Shanghai Science and Technology Committee (19430750100);National Key R&D Program of China (2016YFA0502301 and 2021YFC2301204);Drug development for the newly emerging viral infectious diseases (SIMM010107);Fundamental Research Funds for the Central Universities (2022ZFJH003);Zhejiang Provincial Key Research&Development Program of China (2021C03043 and No.2021C03039).

摘　　要：Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

关 键 词：DRUGS INFECTED treatment 

分 类 号：R97[医药卫生—药品]