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
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: ARTICLES
• 页码范围: 9-23
• 页数: 15页
• 语种: 英文

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.