Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development
作者机构：Department of EndocrinologyBeijing Tongren HospitalCapital Medical UniversityBeijingChina Division of HIV/AIDS and Sex-Transmitted Virus VaccinesInstitute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)BeijingChina Department of Science and TechnologyBeijing Youan HospitalCapital Medical UniversityBeijingChina Division of Animal Model ResearchInstitute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijingChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第4期
页 面：1357-1368页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by grants from the National Key R&D Program of China(2017YFC0909600) National Natural Science Foundation of China(81930019,8151101058,81471014) Scientific Project of Beijing Municipal Science&Technology Commission(D171100002817005) Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201823)
摘 要：To discover new drugs to combat COVID-19,an understanding of the molecular basis of SARS-CoV-2 infection is urgently ***,for the first time,we report the crucial role of cathepsin L(CTSL)in patients with *** circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and ***,SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo,while CTSL overexpression,in turn,enhanced pseudovirus infection in human *** functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry,as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in ***,amantadine,a licensed anti-influenza drug,significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in ***,CTSL is a promising target for new anti-COVID-19 drug development.
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