Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.
Nature
; 594(7862): 246-252, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33845483
ABSTRACT
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-ß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteoma
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Síndrome Respiratória Aguda Grave
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Proteômica
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Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
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Interações Hospedeiro-Patógeno
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SARS-CoV-2
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COVID-19
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha