Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity-Opportunity for Repurposed Chemotherapy of COVID-19 Infection.
COVID-19
bioinformatics
coronavirus
doxorubicin
glyoxalase
methylglyoxal
paclitaxel
proteomics
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
07
2020
accepted:
14
09
2020
entrez:
9
11
2020
pubmed:
10
11
2020
medline:
10
11
2020
Statut:
epublish
Résumé
The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG - residues with predicted or expected low pK
Identifiants
pubmed: 33162891
doi: 10.3389/fphar.2020.585408
pmc: PMC7581855
doi:
Types de publication
Journal Article
Langues
eng
Pagination
585408Informations de copyright
Copyright © 2020 Al-Motawa, Abbas, Wijten, de la Fuente, Xue, Rabbani and Thornalley.
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