Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2  

作　　者：Shaojun Zhang Wenze Huang Lili Ren Xiaohui Ju Mingli Gong Jian Rao Lei Sun Pan Li Qiang Ding Jianwei Wang Qiangfeng Cliff Zhang 

机构地区：[1]MOE Key Laboratory of Bioinformatics,Beijing Advanced Innovation Center for Structural Biology&Frontier Research Center for Biological Structure,Center for Synthetic and Systems Biology,Tsinghua-Peking Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing,China [2]Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [3]Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China [4]Center for Infectious Disease Research,School of Medicine,Tsinghua University,Beijing,China

出　　处：《Cell Research》2022年第1期9-23,共15页细胞研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(91740204,91940306,and 31761163007 to Q.C.Z.,81930063 to J.W.,32070153 to Q.D.);the National Key R&D Program of China(2018YFA0107603 and 2019YFA011000 to Q.C.Z.);Tsinghua University Spring Breeze Fund(2020Z99CFY029 to Q.C.Z.,2021Z99CFY030 to Q.D.);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020HY320001 to L.R.);the Tsinghua-Cambridge Joint Research Initiative Fund(2019Z02CAU to Q.C.Z.).

摘　　要：In contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection,few studies have examined interactions between host factors and viral RNAs(vRNAs).Here,we profiled vRNA–host protein interactomes for three RNA virus pathogens(SARS-CoV-2,Zika,and Ebola viruses)using ChIRP-MS.Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection.In particular,SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation.Our interactome-informed drug repurposing efforts identified several FDA-approved drugs(e.g.,Cepharanthine)as broad-spectrum antivirals in cells and hACE2 transgenic mice.A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant.Thus,our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA-host protein interactome perspective.

关 键 词：DRUGS VIRAL INTERACT 

分 类 号：R563.1[医药卫生—呼吸系统]