ArticlemBio2019
Didehydro-Cortistatin A Inhibits HIV-1 by Specifically Binding to the Unstructured Basic Region of Tat.
Article in mBio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 83 citations in OpenAlex.
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580.PLoS pathogens · 2026Article
- Combining spironolactone to antiretroviral therapy accelerates HIV decay in humanized mice.Emerging microbes & infections · 2025Article
- HIV-1 Tat: Molecular Switch in Viral Persistence and Emerging Technologies for Functional Cure.International journal of molecular sciences · 2025Review
- BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.Nature communications · 2025Article
- Human chromatin remodelers regulating HIV-1 transcription: a target for small molecule inhibitors.Epigenetics & chromatin · 2025Review
- Heat shock protein 90 is a chaperone regulator of HIV-1 latency.PLoS pathogens · 2025Article
- FBXO45 restricts HIV-1 replication by inducing SQSTM1/p62-mediated autophagic degradation of Tat.Journal of virology · 2025Article
- Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication.Life (Basel, Switzerland) · 2025Review
- Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025.Pathogens & immunity · 2025Article
- The role of Tat in HIV latency and reactivation.Frontiers in immunology · 2025Review
- CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells.iScience · 2024Article
- Transcriptional and methylation outcomes of didehydro-cortistatin A use in HIV-1-infected CD4Life science alliance · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.Acta pharmacologica Sinica · 2024Article
- Targeting Viral Transcription for HIV Cure Strategies.Microorganisms · 2024Review
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
- Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.Viruses · 2023Article
- Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
The intrinsically disordered HIV-1 Tat protein binds the viral RNA transactivation response structure (TAR), which recruits transcriptional cofactors, amplifying viral mRNA expression. Limited Tat transactivation correlates with HIV-1 latency. Unfortunately, Tat inhibitors are not clinically available. The small molecule didehydro-cortistatin A (dCA) inhibits Tat, locking HIV-1 in persistent latency, blocking viral rebound. We generated chemical derivatives of dCA that rationalized molecular docking of dCA to an active and specific Tat conformer. These revealed the importance of the cycloheptene ring and the isoquinoline nitrogen's positioning in the interaction with specific residues of Tat's basic domain. These features are distinct from the ones required for inhibition of cyclin-dependent kinase 8 (CDK8), the only other known ligand of dCA. Besides, we demonstrated that dCA activity on HIV-1 transcription is independent of CDK8. The binding of dCA to Tat with nanomolar affinity alters the local protein environment, rendering Tat more resistant to proteolytic digestion. dCA thus locks a transient conformer of Tat, specifically blocking functions dependent of its basic domain, namely the Tat-TAR interaction; while proteins with similar basic patches are unaffected by dCA. Our results improve our knowledge of the mode of action of dCA and support structure-based design strategies targeting Tat, to help advance development of dCA, as well as novel Tat inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.