Dilazep synergistically reactivates latent HIV-1 in latently infected cells

Zeng, Hulie; Liu, Sijie; Wang, Pengfei; Qu, Xin; Ji, Haiyan; Wang, Xiaohui; Zhu, Xiaoli; Song, Zhishuo; Yang, Xinyi; Ma, Zhongjun; Zhu, Huanzhang

doi:10.1007/s11033-014-3662-z

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…Anti-viral effect against species associated with upper respiratory tract infection (URTIs) or known to cause acute sore throat observed with the drug hexylresorcinol (Shephard & Zybeshari, 2015). Alprazolam and dilazep found to be effective in Influenza Virus Infection and HIV, respectively, and danaprevir is a hepatitis C virus protease inhibitor (Freire-Garabal et al, 1993;Zeng et al, 2014;Gane et al, 2014). Apart from that, the calmodulin antagonist and topoisomerase I inhibitor have reported antiviral activity against the Dengue virus and HIV infection (Bautista-Carbajal, 2017;Showalter & Blair, 2016).…”

Section: Discussionmentioning

confidence: 99%

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Loganathan

Ramachandran

Shankaran

et al. 2020

PeerJ

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Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. Methods We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. Results The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.

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Section: Discussionmentioning

confidence: 99%

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Loganathan

Ramachandran

Shankaran

et al. 2020

PeerJ

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“…J-Lat C11 cells which were generated and used in our lab [ 26 , 28 , 48 – 50 ], were latently infected Jurkat cells encoded to express green fluorescent protein (GFP) as a marker for Tat-driven HIV long terminal repeats (LTR) expression. J-Lat A10.6 cells were obtained from NIH AIDS Reagent Program.…”

Section: Methodsmentioning

confidence: 99%

The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells

Pan

Shen

et al. 2017

Oncotarget

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The long-lived latent HIV-1 reservoir is the major barrier for complete cure of Acquired Immune Deficiency Syndrome (AIDS). Here we report that a novel bromodomain and extraterminal domain (BET) inhibitor bromosporine which can broadly target BETs, is able to potently reactivate HIV-1 replication in different latency models alone and more powerful when combined with prostratin or TNF-α. Furthermore, the treatment with bromosporine induced HIV-1 full-length transcripts in resting CD4+ T cells from infected individuals with suppressive antiretroviral therapy (ART) ex vivo, with no obvious cytotoxicity or global activation of T cell. Finally, our data suggest that Tat plays a critical role in the bromosporine-mediated reactivation of latent HIV-1, which involved the increase of CDK9 T-loop phosphorylation. In summary, we found that the BET inhibitor bromosporine, alone or with other activators, might be a candidate for future HIV-1 eradication strategies.

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“…Importantly, combinations of reagents with different mechanisms of action have shown efficacy. For example, the nucleoside transport inhibitor dilazep, HDAC inhibitor MC1293, and arsenic trioxide (As2O3) all synergistically reactivate latent HIV-1 with other activators, providing a new HIV latency reactivation strategy [47–49] (Table 1). …”

Section: Strategies For Sterilizing Hiv Curementioning

confidence: 99%

Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

Wang

et al. 2017

BioMed Research International

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Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4+ T cells. Currently, two types of HIV cures are in development: a “sterilizing cure” and a “functional cure.” A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment. Based on these concepts, significant progress has been made in different areas. This review focuses on recent advancements and future prospects for HIV cures.

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Dilazep synergistically reactivates latent HIV-1 in latently infected cells

Cited by 4 publications

References 42 publications

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach

The bromodomain and extraterminal domain inhibitor bromosporine synergistically reactivates latent HIV-1 in latently infected cells

Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

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