Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038362 (
stomatitis
)
8,852
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular
stomatitis
virus (VSV). The mechanism of action occurs through activation of
REDD1
expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1-TSC2 complex. The antiviral activity of naphthalimides was abolished in
REDD1
(-/-) cells. Inhibition of
REDD1
expression by viruses resulted in activation of the mTORC1 pathway.
REDD1
(-/-) cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of
REDD1
downregulated the amount of viral protein. Thus,
REDD1
is a new host defense factor, and chemical activation of
REDD1
expression represents a potent antiviral intervention strategy.
...
PMID:Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor. 2190 97
