Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2

Author:

Xu GangORCID,Wu Yezi,Xiao Tongyang,Qi Furong,Fan Lujie,Zhang Shengyuan,Zhou Jian,He Yanhua,Gao Xiang,Zeng Hongxiang,Li Yunfei,Zhang ZhengORCID

Abstract

AbstractThe Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn’t code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets.

Funder

China National Funds for Distinguished Young Scientists

National Natural Science Foundation of China

Shenzhen Science and Technology Innovation Commission

Guangdong Science and Technology Department

the Central Charity Fund of Chinese Academy of Medical Science

the National key research and development program

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics

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