Mapping the SARS-CoV-2-Host Protein-Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics.
A549 Cells
Angiotensin-Converting Enzyme 2
/ metabolism
Antiviral Agents
/ therapeutic use
COVID-19
/ pathology
Cell Line
Drug Repositioning
HEK293 Cells
Humans
Mass Spectrometry
Protein Interaction Mapping
Protein Interaction Maps
SARS-CoV-2
/ drug effects
Serine Endopeptidases
/ metabolism
Spike Glycoprotein, Coronavirus
/ metabolism
Virus Internalization
/ drug effects
Virus Replication
/ drug effects
COVID-19 Drug Treatment
COVID-19
SARS-CoV-2
affinity-purification mass spectrometry
antiviral
drug repurposing
emerging
protein–protein interaction
proteomics
proximity-dependent biotin labeling (BioID)
virus
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
07 Jan 2021
07 Jan 2021
Historique:
received:
17
12
2020
revised:
02
01
2021
accepted:
04
01
2021
entrez:
12
1
2021
pubmed:
13
1
2021
medline:
21
1
2021
Statut:
epublish
Résumé
Protein-protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage to obtain a "high resolution" view of virus-host interactions has come true. In fact, the rapidly expanding approaches of mass spectrometry (MS)-based proteomics in the study of PPIs provide efficient tools to identify a significant number of potential drug targets. Generation of PPIs maps by affinity purification-MS and by the more recent proximity labeling-MS may help to uncover cellular processes hijacked and/or altered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing promising therapeutic targets. The possibility to further validate putative key targets from high-confidence interactions between viral bait and host protein through follow-up MS-based multi-omics experiments offers an unprecedented opportunity in the drug discovery pipeline. In particular, drug repurposing, making use of already existing approved drugs directly targeting these identified and validated host interactors, might shorten the time and reduce the costs in comparison to the traditional drug discovery process. This route might be promising for finding effective antiviral therapeutic options providing a turning point in the fight against the coronavirus disease-2019 (COVID-19) outbreak.
Identifiants
pubmed: 33430309
pii: ijms22020532
doi: 10.3390/ijms22020532
pmc: PMC7825748
pii:
doi:
Substances chimiques
Antiviral Agents
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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