Abstract
Despite the availability of vaccines and approved therapeutics, the COVID-19 pandemic continues to rise owing to the emergence of newer variants. Several multi-omics studies have made available extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their ensuing effect on the biochemical and cellular dynamics is critical to expanding the current knowledge on the host response to SARS-CoV-2 infections. Here, employing unbiased global transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV-2 Norway/Trondheim-S15 strain induces time-dependent alterations in the induction of type I IFN response, activation of DNA damage response, dysregulated Hippo signaling, among others. We provide evidence for the interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings serve as a resource of potential targets that can aid in designing novel host-directed therapeutic strategies.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- AGC
- Automatic Gain Control
- ATCC
- American Type Culture Collection
- BCA
- Bicinchoninic acid
- BSA
- Bovine Serum Albumin
- CRISPR
- Clustered Regularly Interspaced Short Palindromic Repeats
- DEG
- Differentially Expressed Genes
- DMEM
- Dulbecco’s Modified Eagle Medium
- DTT
- Dithiothreitol
- FASP
- Filter-Aided Sample Preparation
- FBS
- Fetal Bovine Serum
- FDA
- Food and Drug Administration
- FDR
- False Discovery Rate
- HCD
- Higher Energy Collision Dissociation
- H-ESI
- Heated Electrospray ionization
- HILIC
- Hydrophilic interaction liquid chromatography
- hpi
- hours post-infection
- IAA
- Iodoacetamide
- ISG
- Interferon Stimulated Genes
- KEGG
- Kyoto Encyclopedia of Genes and Genomes
- LC-MS/MS
- Liquid Chromatography Tandem Mass Spectrometry
- MDS
- Multi-Dimensional Scaling
- MOI
- Multiplicity of Infection
- MOPS
- 3-(N-morpholino)propanesulfonic acid
- mRNA
- messenger Ribo Nucleic Acid
- MSEA
- Metabolite set enrichment analysis
- NCE
- Normalized collision energy
- NGS
- Next-Generation Sequencing
- PCA
- Principal component analysis
- PDB
- Protein Data Bank
- PPI
- Protein-protein interaction
- PSM
- Peptide-spectrum match
- PTM
- Post-Translational Modification
- QC
- Quality Control
- RSD
- Relative standard deviation
- SARS-CoV-2
- Severe Acute Respiratory Syndrome Coronavirus 2
- SCX
- Strong cation exchange
- SDS
- Sodium dodecyl-sulfate
- SPE
- Solid-Phase Extraction
- TBS
- Tris-Buffered Saline
- TEAB
- Triethylammonium bicarbonate
- TFA
- Trifluoroacetic acid
- TMT
- Tandem mass tag
- UHPLC
- Ultra-high performance liquid chromatography