Interferon-stimulated gene products as regulators of central carbon metabolism.
FEBS J
; 288(12): 3715-3726, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-923390
ABSTRACT
In response to viral infections, the innate immune system rapidly activates expression of several interferon-stimulated genes (ISGs), whose protein and metabolic products are believed to directly interfere with the viral life cycle. Here, we argue that biochemical reactions performed by two specific protein products of ISGs modulate central carbon metabolism to support a broad-spectrum antiviral response. We demonstrate that the metabolites generated by metalloenzymes nitric oxide synthase and the radical S-adenosylmethionine (SAM) enzyme RSAD2 inhibit the activity of the housekeeping and glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). We discuss that this inhibition is likely to stimulate a range of metabolic and signalling processes to support a broad-spectrum immune response. Based on these analyses, we propose that inhibiting GAPDH in individuals with deteriorated cellular innate immune response like elderly might help in treating viral diseases such as COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
S-Adenosylmethionine
/
Carbon
/
Proteins
/
Interferons
Limits:
Humans
Language:
English
Journal:
FEBS J
Journal subject:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Febs.15625
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