分子免疫药理学（郑永唐）知识库

In a previous study the small molecule SJP-L-5 that inhibits HIV replication, has been shown to blockuncoating of the viral capsid. Continued study showed that SJP-L-5 might hinder HIV capsid uncoatingby blocking the completion of reverse transcription. However, to date, the mechanism has not beenfully elucidated. Here, the effects of SJP-L-5 for reverse transcription were explored via quantitativePCR, DIG-labelled ELISA, fluorescent resonance energy transfer, and Southern blot assays. We alsoanalyzed the resistance profile of this compound against reverse transcriptase. Our results show thatSJP-L-5 preferentially inhibits PPT primed plus-strand DNA synthesis (EC 50 = 13.4 ± 3.0 μM) overRNA primed minus-strand DNA synthesis (EC 50 > 3,646 μM), resulting in formation of five segmentedplus-strand DNA and loss of HIV DNA flap, suggesting failure of both nuclear import and integration.Moreover, resistance study evidenced that SJP-L-5 requires the amino acid residues Val108 andTyr181 to exert an inhibitory effect. These results indicate SJP-L-5 as a new non-nucleoside reversetranscriptase inhibitor that inhibits HIV-1 polypurine tract primed plus-strand DNA synthesis, initiatingHIV-1 down-stream plus-strand DNA synthesis at multiple sites under drug pressure.