Virtual screening for natural product inhibitors of HIV-1 integrase.

Abstract

Since there is no human homolog of this enzyme, HIV-1 integrase (IN) represents a rational and important target for treating HIV infection and preventing AIDS. The 3D structure of full-length HIV-1 IN, either separately or in complex with its inhibitors, has been lacking. Thus, scarce information about the interactions between the HIV-1 IN and its inhibitors can be referenced. To more rationally design potent HIV-1 IN inhibitors, we have previously constructed a model of the full-length HIV-1 IN tetramer and a model of the protein-viral DNA complex, as well as the pharmacophore model of HIV-1 IN strand transfer inhibitors (INSTIs). In this paper, the pharmacophore model of INSTIs was used as a 3D query to screen the Traditional Chinese Medicine Database (TCMD). The hit compounds were further filtered by Lipinski's Rule of Five and docking study to refine the retrieved hits. Finally, 9 suitable ligands with similar structures belonging to the thioglycosides were selected. Subsequent molecular dynamics simulation showed that these compounds had interactions with HIV-1 IN binding site and their possible function as IN inhibitors was discussed.

• Authors: Shi-Kun Ma, Ke-Zhu Wu, Ai-Xiu Li
• Journal: Interdisciplinary sciences, computational life sciences (Interdiscip Sci) Vol. 3 Issue 1 Pg. 17-21 (Mar 2011) ISSN: 1867-1462 [Electronic] Germany
• PMID: 21369883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• HIV Integrase Inhibitors
• Ligands
• Thioglycosides
• HIV Integrase
• p31 integrase protein, Human immunodeficiency virus 1

Topics

• Binding Sites
• Drugs, Chinese Herbal (chemistry)
• HIV Integrase (chemistry)
• HIV Integrase Inhibitors (chemistry)
• Ligands
• Models, Molecular
• Protein Structure, Tertiary
• Thioglycosides (chemistry)