HIV Inhibitors Research Based On Virtual Screening

AIDS is one of the most serious diseases which threaten people's health and social progress. To seek new lead compounds with high anti-HIV activity, natural products are modified to improve activity, reduce side effects and increase bioavailability.Based on relative references and activity data, 237 stilbene derivatives are designed. Inorder to study the effect of aromatic nitrogen heterocycle on the bioactivity, one benzene ring of the core structure is substituted with indole, pyrrole and imidazole. The substituents of aza-ring are mainly amino groups. To thr drug targets relating to viral infection, the target screening is done on the TarFisDock. HIV protease is selected as the highly active target. Using computer-aided drug design method, the designed molecules are docked with HIV protease and HIV reverse transcriptase respectively. The interaction between small molecules and the two targets is analyzed.The target screening shows that HIV protease ranks first of all targets dramatically. The docking between HIV protease and 237 molecules are then performed to confirm the reliability of the results. Based on Lipinski rules, drug-like of molecules are predicted. Effects of some physicochemical properties on the binding energy score, such as molecular weight, molecular volume, rotatable bond, octanol/water partition coefficient, hydrogen bonds formed between small molecules and protein are explored. And molecular structure factors affecting docking results are also discussed. Screening results suggest that HIV protease may be the highly active target of aza-stilbene derivatives to inhibit HIV, especially for styryl indole derivatives.To investigate the dual targets inhibitory property of aza-stilbene derivatives, the designed molecules are docked to the non-nucleotide inhibitor bingding site of HIV reverse transcriptase. The result shows that molecular volume is important. A part of molecules get bad energy scores for their big molecular volume.Based on the flavonoid 6-21 which can work on HFV-1 Vif, sulfonic group is used in structure modification of flavonoids to improve molecular water-solubility. Test set, composed of natural flavonoids and their sulfonic derivatives, is used to locate the potential active site for thr design of new inhibitors. To accomplish molecular docking between flavonoids and Vif protein, three dimensional of Vif is modeled and its active site is predicted. The predicted site is relative to the domain where Vif binds with APOBEC3G. So it's reliable to some extent.