Important note: Information in this article was accurate in May 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, May 3, 1999
Daniel J. DeNoon, Senior Editor
New studies show that the inhibitors, isolated from the medicinal plants of the Kallawaya people of Bolivia, target the core region of retroviral integrase. These dicaffeoylquinic acids (DCQAs) inhibit HIV replication at concentrations well below cytotoxic levels (see AIDS Weekly Plus, January 25, 1999).
In their latest series of studies, researcher Kai Zhu of the University of California, Los Angeles and colleagues report that DCQAs specifically inhibit retroviral integrases and have no effect on other DNA-modifying enzymes and phosphoryl-transferases.
"The activity and specificity of DCQAs will be useful in understanding the biological function and biochemical property of integrase and are promising leads for the development of a new class of anti-HIV drugs," Zhu et al. wrote.
Zhu et al. reported the findings in the Journal of Virology ("Irreversible Inhibition of Human Immunodeficiency Virus Type 1 Integrase by Dicaffeoylquinic Acids," J Virol 1999 Apr;73(4):3309-16.
The DCQAs and related compounds under consideration by Zhu et al. included L-chicoric acid (technically a dicaffeoyltartaric acid or DCTA), chlorogenic acid, 3,4-dicaffeoylquinic acid, and 1-methoxy-3,5-dicaffeoylquinic acid.
A possible drawback to the therapeutic use of these drugs is that they inhibit HIV only when preincubated with the virus or when added to cell cultures at the same time as virus.
"Why such a preincubation is required is unclear," the authors noted in a previous study (McDougall, B. et al., Antimic Ag Chem, 1998;42(1):140-6).
Nevertheless, their long-term goal remains the development of a new class of anti-HIV drugs for use in combination with protease and/or reverse-transcriptase inhibitors.
This work was supported National Institutes of Health grants and by the Brian Reese AIDS Memorial Fund.
The corresponding author for this study is Samson A. Chow, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, 23-133 CHS, 10833 Le Conte Ave., Los Angeles, California 90095. Phone: (310) 825-9600. Fax: (310) 825-6267. Email: <schow@mednet.ucla.edu>.
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