ArticleNature communications2025
BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- BRD proteins in human retroviral infection: emerging evidence from HIV-1 and future perspectives for HTLV-1.Molecular biology reports · 2026Review
- The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency.Microbiology spectrum · 2026Article
- Central Nervous System HIV Persistence and Clinical Consequences During Suppressive ART.Current HIV/AIDS reports · 2026Review
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580.PLoS pathogens · 2026Article
- World free HIV: the novel therapeutic approaches for eliminating latent HIV infection.Virology journal · 2026Review
- Epigenetic regulation of HIV-1 transcription: insights into latency mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Host restriction factors and p17-Driven inflammaging in HIV-1: From molecular pathogenesis to functional cure.AIMS microbiology · 2026Review
- Beyond monotherapy: Combination therapies for HIV-1 cure through joint application of neutralizing antibodies, genome editing, and reservoir management.Infectious medicine · 2025Review
- Targeting HIV myeloid and central nervous system reservoirs for HIV cure.Current opinion in HIV and AIDS · 2025Review
- Retrointegration2023-Papers from the 7th International Conference on Retroviral Integration.Viruses · 2025Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The persistence of HIV-1 in a latent state within long-lived immune cells remains a major barrier to a cure for HIV-1 infection. The "block-and-lock" strategy aims to silence the HIV-1 provirus permanently using latency promoting agents (LPAs). LEDGINs, a well-known class of LPAs, inhibit the interaction between viral integrase and LEDGF/p75, reducing viral integration and retargeting the provirus to regions resistant to reactivation. However, proximity to enhancers may still permit residual transcription. Given BRD4's central role in the enhancer biology, we now test two BRD4 modulators, JQ1 and ZL0580. Mechanistic studies reveal that JQ1 and ZL0580 have contrasting effects on Tat-dependent HIV-1 transcription, resulting in JQ1 promoting viral reactivation and ZL0580 inducing transcriptional silencing. Combining ZL0580 with LEDGINs has an additive effect in blocking HIV-1 transcription and reactivation, in both cell lines and primary cells. These findings demonstrate the potential of ZL0580 to enhance the block-and-lock cure strategy.
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