SARS-CoV-2 helicase NSP13 hijacks the host protein EWSR1 to promote viral replication by enhancing RNA unwinding activity
作者机构：Institute for HepatologyNational Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical ScienceShenzhenGuangdong ProvinceChina Guangdong Key Laboratory for Anti-Infection Drug Quality EvaluationShenzheGuangdong ProvinceChina
出 版 物：《Infectious Medicine》 (感染医学（英文）)
年 卷 期：2022年第1卷第1期
页 面：7-16页
学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学]
基 金：This work was supported by grants from the Na-tional Science Fund for Distinguished Young Schol-ars(82025022) the Central Charity Fund of Chinese Academy of Medical Science(2020-PT310-009) the Sci-ence and Technology Innovation Committee of Shenzhen Municipality(2020A1111350032) the China Post-doctoral Science Foundation(2021M693359)
摘 要：Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged in December 2019 and has led to a global coronavirus disease 2019(COVID-19)***,incomplete understanding of how SARS-CoV-2 arrogates the host cell to establish its life cycle has led to slow progress in the development of effective ***:In this study,we found that SARS-CoV-2 hijacks the host protein EWSR1(Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1)to promote the activity of its helicase NSP13 to facilitate viral ***13 is highly conserved among coronaviruses and is crucial for virus replication,providing chemical energy to unwind viral RNA replication *** with different SARS-CoV-2 NSP13 inhibitors in multi-ple cell lines infected with SARS-CoV-2 effectively suppressed SARS-CoV-2 *** affinity-purification mass spectrometry,the RNA binding protein EWSR1 was then identified as a potent host factor that physically associated with ***,silencing EWSR1 dramatically reduced virus replication at both viral RNA and protein ***,EWSR1 was found to bind to the NTPase domain of NSP13 and potentially enhance its dsRNA unwinding ***:Our results pinpoint EWSR1 as a novel host factor for NSP13 that could potentially be used for drug repurposing as a therapeutic target for COVID-19.
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