HIV Integrase Inhibitors

Publication Title: 
Planta Medica

The bioassay-directed isolation of Terminalia chebula fruits afforded four human immunodeficiency virus type 1 (HIV-1) integrase inhibitors, gallic acid ( 1) and three galloyl glucoses ( 2 - 4). In addition, four flavonol glycoside gallates ( 5 - 8) from Euphorbia pekinensis containing the galloyl moiety also showed the inhibitory activity at a level comparable to those of 2 - 4.

Author(s): 
Ahn, Mi-Jeong
Kim, Chul Young
Lee, Ji Suk
Kim, Tae Gyun
Kim, Seung Hee
Lee, Chong-Kyo
Lee, Bo-Bin
Shin, Cha-Gyun
Huh, Hoon
Kim, Jinwoong
Publication Title: 
Biochemical and Biophysical Research Communications

We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-D116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition.

Author(s): 
Lee-Huang, Sylvia
Huang, Philip Lin
Zhang, Dawei
Lee, Jae Wook
Bao, Ju
Sun, Yongtao
Chang, Young-Tae
Zhang, John
Huang, Paul Lee
Publication Title: 
Biochemical and Biophysical Research Communications

We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core.

Author(s): 
Lee-Huang, Sylvia
Huang, Philip Lin
Zhang, Dawei
Lee, Jae Wook
Bao, Ju
Sun, Yongtao
Chang, Young-Tae
Zhang, John
Huang, Paul Lee
Publication Title: 
Journal of Molecular and Cellular Cardiology

HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl(-) current (I(Cl,swell)) is activated by ROS, we tested whether HIV PI stimulate I(Cl,swell) in ventricular myocytes. Ritonavir and lopinavir elicited outwardly rectifying Cl(-) currents under isosmotic conditions that were abolished by the selective I(Cl,swell)-blocker DCPIB.

Author(s): 
Deng, Wu
Baki, Lia
Yin, Jun
Zhou, Huiping
Baumgarten, Clive M.
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