Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

By Alexey Stukalov, V. Girault, V. Grass, Valter Bergant, Ozge Karayel, C. Urban, Darya A. Haas, Yiqi Huang, L. Oubraham, Anqi Wang and 18 more. Nature, 2020

631 citations recorded by the source corpus.

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1–10. Integration of such datasets to obtain a holistic view of virus–host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2. Multi-omics profiling of effects of SARS-CoV-2 and SARS-CoV on A549, a lung-derived human cell line, produces a dataset enabling identification of common and virus-specific mechanisms of infection.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/006c69d5d26577104425656690c84d1c021dac20

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

H. Qi
S. Tao
Hong Chen
Yun-xiao Zheng
Xue-ning Wang
Jia-Xuan Xie
Ze-Guang Han
Yang Li

Citations in the corpus

SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70 (2020, background): “In addition, there is also a preprint article that indicates that SARS-CoV-2 Orf9b, Orf3, Orf6, Orf7a, and Orf7b can suppress IFN-I responses to different extents.(15) There are two possible explanations how Orf9b inhibits IFN-I responses through interacting with TOM70.”