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Since the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug-resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using Nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. The compound 7b, that had the highest selectivity index (SI = 38,215), is more potent than Nevirapine and 18. These results suggest that introduction of halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, m-substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with improved antiviral efficacy and drug-resistance profile.

Though HIV-1 CRF07_BC rapidly spread in China, there have been few reports about this subtype since its first genetic characterization nearly 10 years ago. It was urgent and necessary to know the current gene variation of circulating CRF07_BC strains. Xinjiang was the main region for the CRF07_BC epidemic and also an ideal region for research on the viral gene evolution. The strains of Ulumuqi and Yili in Xinjiang were isolated, cloned, and sequenced in this study. Analyses of phylogenetic, potential CTL epitopes and N-glycosites were preformed simultaneously. New CRF07_BC isolates showed higher genetic diversity and more potential N-glycosites than old isolates. It was interesting that although the env and nef genes are highly variable, highly conserved potential CTL epitopes and N-glycosites were found in deduced gp120 V3 and Nef product of all CRF07_BC isolates. The analysis of the sequences provides some valuable information on the investigation of the epidemiology and on vaccine development.

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