The evaluation of catechins that contain a galloyl moiety as potential HIV-1 integrase inhibitors.
Four catechins with the galloyl moiety, including catechin gallate (CG), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), and epicatechin gallate (ECG), were found to inhibit HIV-1 integrase effectively as determined by our ELISA method. In our docking study, it is proposed that when the HIV-1 integrase does not combine with virus DNA, the four catechins may bind to Tyr143 and Gln148, thus altering the flexibility of the loop (Gly140-Gly149), which could lead to an inhibition of HIV-1 integrase activity. In addition, after combining HIV-1 integrase with virus DNA, the four catechins may bind between the integrase and virus DNA, consequently, disrupt this interaction. Thus, the four catechins may reduce the activity of HIV-1 integrase by disrupting its interaction with virus DNA. The four catechins have a highly cooperative inhibitory effect (IC₅₀=0.1 μmol/L). Our study suggests that catechins with the galloyl moiety could be a novel and effective class of HIV-1 integrase inhibitors.
Jiang
Fan
F
Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, 28 Fu Xing Road, Hai Dian District, 100853 Beijing, China.
Chen
Wei
W
Yi
Kejia
K
Wu
Zhiqiang
Z
Si
Yiling
Y
Han
Weidong
W
Zhao
Yali
Y
D000163:Acquired Immunodeficiency Syndrome / Q000191:economics / Q000201:enzymology / Q000517:prevention & control*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000191:economics / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000191:economics / Q000494:pharmacology*; D004279:DNA, Viral / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology; D000068898:Raltegravir Potassium
D019380:Anti-HIV Agents; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; C417940:gallocatechin gallate; D000068898:Raltegravir Potassium; C417939:catechin gallate; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1