HIV latency reversal agents: A potential path for functional cure?

Lopes, Juliana Romano; Chiba, Diego Eidy; Santos, Jean Leandro dos

doi:10.1016/j.ejmech.2021.113213

Cited by 6 publications

(4 citation statements)

References 111 publications

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“…INSTIs could also be employed along with latency reversing agents (LRA) (336-341) (Figure 20) are being investigated against viral infected CD4 + T cell to forcefully omit the virus to get detectible by ART drugs. [115,116,117,118]…”

Section: Challenges Involved In Hiv Therapy and Instismentioning

confidence: 99%

Development of Synthetic Approaches Towards HIV Integrase Strand Transfer Inhibitors (INSTIs)

et al. 2022

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A clear and precise report on synthetic methods for INSTIs and their intermediates are provided in the present work. HIV Integrase strand transfer inhibitors (INSTIs), a class of antiretroviral agents employed to treat HIV infected patients are placed as the second option of treatment after nucleosides. As INSTIs are employed as first line therapy to newly infected HIV positive individuals, thus synthetic routes must be easily accessible to the medicinal chemists towards lead optimization or process development. The current perspective elaborates synthetic routes of first to next generation INSTIs investigated in two decades of research and their development efforts. Further, drug resistance occurred by mutations against usage of INSTI drugs with respect to their generation also discussed. Later, discussion about synthetic development and investigation of next generation INSTIs against drug resistance HIV infections also covers to fill the gap between first/second generation INSTIs. The current perspective will draw attention of medicinal chemists and multi‐disciplinary researchers in HIV drug discovery.

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Section: Challenges Involved In Hiv Therapy and Instismentioning

confidence: 99%

Development of Synthetic Approaches Towards HIV Integrase Strand Transfer Inhibitors (INSTIs)

et al. 2022

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“…Among HDAC classes, it seems that those belonging to class I, mainly HDAC-1, -2, and -3, have important roles against DNA and RNA viruses [8]. HDAC inhibitors have also been investigated for integrative retroviruses (HIV and human T-cell leukemia virus type 1, HTLV-1) infections, as latency reversal agents (LRA), exploring the 'Kick and Kill' approach [9][10][11]. According to this strategy, also known as 'shock and kill', the latent viral reservoir could, in theory, be purged in two steps.…”

Section: Introductionmentioning

confidence: 99%

“…This drug exhibited IC 50 values for human HDAC-1, HDAC-2, and HDAC-3 of 0.9 µM, 0.9 µM, and 1.2 µM, respectively [5][6][7][8]. The selectivity for HDAC-1 and HDAC-2 inhibition could be improved by the inclusion of heteroaromatics that occupies the additional 14 Å pocket present in both enzymes [5][6][7][8]10]. Here, we investigated the effect of thiophene (2) and 3,5-dimethyloxazole (3) insertion in the prototype (1) to improve the inhibition of HDAC-1 and -2.…”

Section: Introductionmentioning

confidence: 99%

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Design and Synthesis of Hybrid Compounds as Epigenetic Modifiers

et al. 2021

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Epigenetic modifiers acting through polypharmacology mechanisms are promising compounds with which to treat several infectious diseases. Histone deacetylase (HDAC) enzymes, mainly class I, and extra-terminal bromodomains (BET) are involved in viral replication and the host response. In the present study, 10 compounds were designed, assisted by molecular docking, to act against HDAC class I and bromodomain-4 (BRD4). All the compounds were synthesized and characterized by analytical methods. Enzymatic assays were performed using HDAC-1, -4, and -11 and BRD4. Compounds (2–10) inhibited both HDAC class I, mainly HDAC-1 and -2, and reduced BRD4 activity. For HDAC-1, the inhibitory effect ranged from 8 to 95%, and for HDAC-2, these values ranged from 10 to 91%. Compounds (2–10) decreased the BRD4 activity by up to 25%. The multi-target effects of these compounds show desirable properties that could help to combat viral infections by acting through epigenetic mechanisms.

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Atom-based 3D-QSAR and DFT analysis of 5‐substituted 2‐acylaminothiazole derivatives as HIV-1 latency-reversing agents

Khan

2022

Journal of Biomolecular Structure and Dynamics

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HIV latency reversal agents: A potential path for functional cure?

Cited by 6 publications

References 111 publications

Development of Synthetic Approaches Towards HIV Integrase Strand Transfer Inhibitors (INSTIs)

Development of Synthetic Approaches Towards HIV Integrase Strand Transfer Inhibitors (INSTIs)

Design and Synthesis of Hybrid Compounds as Epigenetic Modifiers

Atom-based 3D-QSAR and DFT analysis of 5‐substituted 2‐acylaminothiazole derivatives as HIV-1 latency-reversing agents

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