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.
【저자키워드】 proteomics, Cell Biology, 【초록키워드】 viruses, SARS-CoV-2, viral infection, translation, B.1.351, Infection, host response, hACE2, Protein, Viral, pathogen, RNA viruses, Research, protein interaction, broad-spectrum antivirals, Cepharanthine, Pathogens, Zika, Ebola, Viral RNA, RNA virus, utility, Interaction, Analysis, host cells, host cell, Comparative, Factor, Trifluoperazine, viral RNAs, FDA-approved drug, B.1.351 variant, Perspective, transgenic mice, effort, vRNA, SARS-CoV-2 B.1.351 variant, Host, broad-spectrum antiviral, Cell, IGF2BP1, bind, examined, promote, restrict, engage, 【제목키워드】 SARS-CoV-2, antiviral drug, Protein, RNA virus, pathogenic,