Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 16, Pages 5043-5051Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm800332m
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Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [1 R21 AI071802]
- National Institutes of Health, Bethesda, Maryland
- Nabi Biopharmaceuticals, Rockville, Maryland
- NIAID
- Intramural AIDS Targeted Antiviral Program (IATAP)
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series of ring expanded nucleoside (REN) analogues were synthesized and screened for inhibition of cellular RNA helicase activity and human immunodeficiency Virus type 1 (HIV-1) replication. We identified two compounds, 1 and 2, that inhibited the ATP dependent activity of human RNA helicase DDX3. Compounds 1 and 2 also Suppressed HIV-I replication in T cells and monocyte-derived macrophages. Neither compound at therapeutic doses was significantly toxic ill ex vivo cell culture or in vivo in mice. Our finding's provide proof-of-concept that a cellular factor, all RNA helicase. Could be targeted for inhibiting HIV-1 replication.
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