Inhibitors of HIV-1 Replication that Inhibit HIV Integrase

HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might be directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-06, Vol.93 (13), p.6326-6331
Main Authors: Robinson, W. Edward, Reinecke, Manfred G., Abdel-Malek, Samia, Jia, Qi, Chow, Samson A.
Format: Article
Language:English
Subjects:
Antiviral Agents - pharmacology
Antivirals
Base Sequence
Caffeic Acids
Cell Line
Cell lines
Cellular biology
Chlorogenic Acid - analogs & derivatives
Chlorogenic Acid - pharmacology
DNA
DNA Nucleotidyltransferases - antagonists & inhibitors
Enzyme Inhibitors - pharmacology
Enzymes
HIV
HIV 1
HIV-1 - enzymology
HIV-1 - physiology
Human immunodeficiency virus
human immunodeficiency virus 1
Humans
Integrases
Medical research
Medical treatment
Molecular Sequence Data
Oligodeoxyribonucleotides
Oligonucleotides
Succinates - pharmacology
Tissue culture techniques
Viral DNA
Virus Replication - drug effects
Viruses
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Summary:HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might be directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic acid, and L-chicoric acid, inhibit HIV-1 integrase in biochemical assays at concentrations ranging from 0.06-0.66 μ g/ml; furthermore, these compounds inhibit HIV-1 replication in tissue culture at 1-4 μ g/ml. The toxic concentrations of these compounds are fully 100-fold greater than their antiviral concentrations. These compounds represent a potentially important new class of antiviral agents that may contribute to our understanding of the molecular mechanisms of viral integration. Thus, the dicaffeoylquinic acids are promising leads to new anti-HIV therapeutics and offer a significant advance in the search for new HIV enzyme targets as they are both specific for HIV-1 integrase and active against HIV-1 in tissue culture.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.13.6326