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Article ; Online: The Involvement of Ubiquitination and SUMOylation in Retroviruses Infection and Latency.

Liang, Taizhen / Li, Guojie / Lu, Yunfei / Hu, Meilin / Ma, Xiancai

2023 Volume 15, Issue 4

Abstract: Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be ... ...

Abstract	Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be temporarily transcriptional silencing in infected cells, which makes retroviral infection incurable. Although many cellular restriction factors interfere with various steps of the life cycle of retroviruses and the formation of viral latency, viruses can utilize viral proteins or hijack cellular factors to evade intracellular immunity. Many post-translational modifications play key roles in the cross-talking between the cellular and viral proteins, which has greatly determined the fate of retroviral infection. Here, we reviewed recent advances in the regulation of ubiquitination and SUMOylation in the infection and latency of retroviruses, focusing on both host defense- and virus counterattack-related ubiquitination and SUMOylation system. We also summarized the development of ubiquitination- and SUMOylation-targeted anti-retroviral drugs and discussed their therapeutic potential. Manipulating ubiquitination or SUMOylation pathways by targeted drugs could be a promising strategy to achieve a "sterilizing cure" or "functional cure" of retroviral infection.
MeSH term(s)	Humans ; Sumoylation ; Ubiquitination ; Retroviridae Infections ; Viral Proteins/metabolism ; Retroviridae/genetics ; Retroviridae/metabolism
Chemical Substances	Viral Proteins
Language	English
Publishing date	2023-04-17
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15040985
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Emerging and state of the art hemagglutinin-targeted influenza virus inhibitors.

Zhang, Qiao / Liang, Taizhen / Nandakumar, Kutty Selva / Liu, Shuwen

Expert opinion on pharmacotherapy

2020 Volume 22, Issue 6, Page(s) 715–728

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Hemagglutinins/therapeutic use ; Humans ; Influenza, Human/drug therapy ; Neuraminidase ; Orthomyxoviridae
Chemical Substances	Antiviral Agents ; Hemagglutinins ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2020-12-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2020.1856814
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nanoparticles and Antiviral Vaccines.

Liu, Sen / Hu, Meilin / Liu, Xiaoqing / Liu, Xingyu / Chen, Tao / Zhu, Yiqiang / Liang, Taizhen / Xiao, Shiqi / Li, Peiwen / Ma, Xiancai

Vaccines

2023 Volume 12, Issue 1

Abstract: Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In ... ...

Abstract	Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines.
Language	English
Publishing date	2023-12-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12010030
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Article ; Online: Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein.

Liang, Taizhen / Xiao, Shiqi / Wu, Ziyao / Lv, Xi / Liu, Sen / Hu, Meilin / Li, Guojie / Li, Peiwen / Ma, Xiancai

Viruses

2023 Volume 15, Issue 8

Abstract: Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence ... ...

Abstract	Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several US FDA-approved drugs and identified phenothiazine derivatives with the ability to potently inhibit the infection of pseudotyped SARS-CoV-2 and distinct variants of concern (VOCs), including B.1.617.2 (Delta) and currently circulating Omicron sublineages XBB and BQ.1.1, as well as pseudotyped SARS-CoV and MERS-CoV. Mechanistic studies suggested that phenothiazines predominantly inhibited SARS-CoV-2 pseudovirus (PsV) infection at the early stage and potentially bound to the spike (S) protein of SARS-CoV-2, which may prevent the proteolytic cleavage of the S protein, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that phenothiazines can serve as a potential broad-spectrum therapeutic drug for the treatment of SARS-CoV-2 infection as well as the infection of future emerging human coronaviruses (HCoVs).
MeSH term(s)	Humans ; SARS-CoV-2 ; Phenothiazines/pharmacology ; COVID-19 ; Spike Glycoprotein, Coronavirus
Chemical Substances	Phenothiazines ; spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2023-07-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081666
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SNW1 interacts with IKKγ to positively regulate antiviral innate immune responses against influenza A virus infection.

Zhang, Qiao / Liang, Taizhen / Gu, Shuyin / Ye, Yilu / Liu, Shuwen

Microbes and infection

2020 Volume 22, Issue 10, Page(s) 576–584

Abstract: The Ski-interacting protein (SNW1) acts as a transcriptional co-regulator associated with mRNA splicing and transcription, cell cycle progression, acute and chronic inflammatory responses, however, its role involved in host antiviral innate immune ... ...

Abstract	The Ski-interacting protein (SNW1) acts as a transcriptional co-regulator associated with mRNA splicing and transcription, cell cycle progression, acute and chronic inflammatory responses, however, its role involved in host antiviral innate immune responses remains to be explored. Here, for the first time, we demonstrated that SNW1 positively regulates the expression of pro-inflammatory cytokines and interferon (IFN) responses induced by influenza A virus (IAV) infection, and further inhibits virus replication by performing SNW1 depletion or overexpression approaches. Furthermore, we showed that reduced interferon beta (IFN-β) expression caused by interfering SNW1 impairs the activation of JAK-STAT pathway in response to IAV or poly I:C. Importantly, by interacting with IKKγ, the regulatory subunit of IκB kinase (IKK) complex, SNW1 promotes IAV-induced activation of NF-κB and phosphorylation of TBK1 kinase, leading to the increase of antiviral effectors interleukin 6 (IL-6), C-X-C motif chemokine 10 (CXCL10), IFN-β and myxovirus resistance protein 1 (MX1). Taken together, our study revealed that SNW1 is an important mediator of host defenses against IAV through the induction of pro-inflammatory factors and IFN signaling, providing novel insights in modulating innate immune responses to protect host from IAV infection.
MeSH term(s)	A549 Cells ; HEK293 Cells ; Humans ; I-kappa B Kinase/metabolism ; Immunity, Innate ; Influenza A virus/physiology ; Interferon-beta/metabolism ; Nuclear Receptor Coactivators/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism ; STAT1 Transcription Factor/metabolism ; Signal Transduction ; Transcription Factor RelA/metabolism ; Virus Replication
Chemical Substances	IKBKG protein, human ; Nuclear Receptor Coactivators ; RELA protein, human ; SNW1 protein, human ; STAT1 Transcription Factor ; Transcription Factor RelA ; Interferon-beta (77238-31-4) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TBK1 protein, human (EC 2.7.11.1) ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2020-08-14
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2020.07.009
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Article ; Online: UHRF1 Suppresses HIV-1 Transcription and Promotes HIV-1 Latency by Competing with p-TEFb for Ubiquitination-Proteasomal Degradation of Tat.

Liang, Taizhen / Zhang, Qiao / Wu, Ziyao / Chen, Pei / Huang, Yifan / Liu, Shuwen / Li, Lin

mBio

2021 Volume 12, Issue 4, Page(s) e0162521

Abstract: HIV-1 remains incurable due to viral reservoirs, which lead to durably latent HIV infection. Identifying novel host factors and deciphering the molecular mechanisms involved in the establishment and maintenance of latency are critical to discover new ... ...

Abstract	HIV-1 remains incurable due to viral reservoirs, which lead to durably latent HIV infection. Identifying novel host factors and deciphering the molecular mechanisms involved in the establishment and maintenance of latency are critical to discover new targets for the development of novel anti-HIV agents. Here, we show that ubiquitin-like with PHD and RING finger domain 1 (UHRF1) modulates HIV-1 5'-long terminal repeat (LTR)-driven transcription of the viral genome as a novel HIV-1 restriction factor. Correspondingly, UHRF1 depletion reversed the latency of HIV-1 proviruses. Mechanistically, UHRF1 competed with positive transcription factor b (p-TEFb) for the binding to the cysteine-rich motifs of HIV-1 Tat via its TTD, PHD, and RING finger domains. Furthermore, UHRF1 mediated K48-linked ubiquitination and proteasomal degradation of Tat in RING-dependent ways, leading to the disruption of Tat/cyclin T1/CDK9 complex and consequential impediment of transcription elongation. In summary, our findings revealed that UHRF1 is an important mediator of HIV-1 latency by controlling Tat-mediated transcriptional activation, providing novel insights on host-pathogen interaction for modulating HIV-1 latency, beneficial for the development of anti-AIDS therapies.
MeSH term(s)	CCAAT-Enhancer-Binding Proteins/genetics ; CCAAT-Enhancer-Binding Proteins/metabolism ; HEK293 Cells ; HIV Infections/virology ; HIV Long Terminal Repeat/genetics ; HIV-1/genetics ; Humans ; Jurkat Cells ; Positive Transcriptional Elongation Factor B/genetics ; Positive Transcriptional Elongation Factor B/metabolism ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Proviruses/genetics ; Transcription, Genetic ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Virus Latency/genetics ; Virus Replication/genetics ; tat Gene Products, Human Immunodeficiency Virus/genetics ; tat Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	CCAAT-Enhancer-Binding Proteins ; tat Gene Products, Human Immunodeficiency Virus ; UHRF1 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Positive Transcriptional Elongation Factor B (EC 2.7.11.-) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2021-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.01625-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: NSP6 inhibits the production of ACE2-containing exosomes to promote SARS-CoV-2 infectivity.

Lv, Xi / Chen, Ran / Liang, Taizhen / Peng, Haojie / Fang, Qiannan / Xiao, Shiqi / Liu, Sen / Hu, Meilin / Yu, Fei / Cao, Lixue / Zhang, Yiwen / Pan, Ting / Xi, Zhihui / Ding, Yao / Feng, Linyuan / Zeng, Tao / Huang, Wenjing / Zhang, Hui / Ma, Xiancai

mBio

2024 Volume 15, Issue 3, Page(s) e0335823

Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes ( ... ...

Abstract	The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019. Importance: The outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.
MeSH term(s)	Humans ; COVID-19/metabolism ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Exosomes/metabolism ; Peptidyl-Dipeptidase A/metabolism ; Antiviral Agents/pharmacology ; Spike Glycoprotein, Coronavirus/metabolism ; Protein Binding
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Antiviral Agents ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03358-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: CPI-203 improves the efficacy of anti-PD-1 therapy by inhibiting the induced PD-L1 overexpression in liver cancer.

Niu, Xiaoge / Wang, Wei / Liang, Taizhen / Li, Shasha / Yang, Chan / Xu, Xinfeng / Li, Lin / Liu, Shuwen

Cancer science

2021 Volume 113, Issue 1, Page(s) 28–40

Abstract: Hepatocellular carcinoma (HCC) is one of the commonest lethal malignancies worldwide, and often diagnosed at an advanced stage, without any curative therapy. Immune checkpoint blockers targeting the programmed death receptor 1 (PD-1) have shown ... ...

Abstract	Hepatocellular carcinoma (HCC) is one of the commonest lethal malignancies worldwide, and often diagnosed at an advanced stage, without any curative therapy. Immune checkpoint blockers targeting the programmed death receptor 1 (PD-1) have shown impressive antitumor activity in patients with advanced-stage HCC, while the response rate is only 30%. Inducible PD-L1 overexpression may result in a lack of response to cancer immunotherapy, which is attributed to a mechanism of adaptive immune resistance. Our study investigated that the overexpression of PD-L1 promoted the invasion and migration of liver cancer cells in vitro, and the induced overexpression of PD-L1 in the tumor microenvironment could weaken the effects of anti-PD-1 immunotherapy in a BALB/c mouse model of liver cancer. CPI-203, a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor, which can potently inhibit PD-L1 expression in vitro and in vivo, combined with PD-1 antibody improved the response to immunotherapy in a liver cancer model. Cell transfection and chromatin immunoprecipitation assay manifested that BRD4 plays a key role in PD-L1 expression; CPI-203 can inhibit PD-L1 expression by inhibiting the BRD4 occupation of the PD-L1 promoter region. This study indicates a potential clinical immunotherapy method to reduce the incidence of clinical resistance to immunotherapy in patients with HCC.
MeSH term(s)	Acetamides/administration & dosage ; Acetamides/pharmacology ; Animals ; Azepines/administration & dosage ; Azepines/pharmacology ; B7-H1 Antigen/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Drug Synergism ; Gene Expression Regulation, Neoplastic/drug effects ; Hep G2 Cells ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/pharmacology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Male ; Mice ; Promoter Regions, Genetic/drug effects ; Transcription Factors/metabolism ; Tumor Escape/drug effects ; Tumor Microenvironment/drug effects ; Up-Regulation/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Acetamides ; Azepines ; B7-H1 Antigen ; BRD4 protein, human ; CD274 protein, human ; CPI203 ; Cell Cycle Proteins ; Immune Checkpoint Inhibitors ; Transcription Factors
Language	English
Publishing date	2021-11-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1347-9032
ISSN (online)	1349-7006
ISSN	1347-9032
DOI	10.1111/cas.15190
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: 3-Hydroxyphthalic Anhydride-Modified Chicken Ovalbumin as a Potential Candidate Inhibits SARS-CoV-2 Infection by Disrupting the Interaction of Spike Protein With Host ACE2 Receptor.

Liang, Taizhen / Qiu, Jiayin / Niu, Xiaoge / Ma, Qinhai / Zhou, Chenliang / Chen, Pei / Zhang, Qiao / Chen, Meiyun / Yang, Zifeng / Liu, Shuwen / Li, Lin

Frontiers in pharmacology

2021 Volume 11, Page(s) 603830

Abstract: The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus ... ...

Abstract	The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.603830
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Article ; Online: A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb.

Liang, Taizhen / Wu, Ziyao / Li, Yibin / Li, Chao / Zhao, Kangni / Qiao, Xinman / Duan, Heng / Zhang, Xuanxuan / Liu, Shuwen / Xi, Baomin / Li, Lin

Biochemical pharmacology

2021 Volume 197, Page(s) 114901

Abstract: The persistence of HIV-1 latent reservoir creates the major obstacle toward an HIV-1 cure. The "shock and kill" strategy aims to reverse HIV-1 proviral latency using latency-reversing agents (LRAs), thus boosting immune recognition and clearance to ... ...

Abstract	The persistence of HIV-1 latent reservoir creates the major obstacle toward an HIV-1 cure. The "shock and kill" strategy aims to reverse HIV-1 proviral latency using latency-reversing agents (LRAs), thus boosting immune recognition and clearance to residual infected cells. Unfortunately, to date, none of these tested LRA candidates has been demonstrated effectiveness and/or safety in reactivation HIV-1 latency. The discovery and development of effective, safe and affordable LRA candidates are urgently needed for creating an HIV-1 functional cure. Here, we designed and synthesized a series of small-molecule phenoxyacetic acid derivatives based on the resveratrol scaffold and found one of them, named 5, 7-dimethoxy-2-(5-(methoxymethyl) furan-2-yl) quinazolin-4(3H)-one (Q205), effectively reactivated latent HIV-1 in latent HIV-1-infected cells without a corresponding increase in induction of potentially damaging cytokines. The molecular mechanism of Q205 is shown to increase the phosphorylation of the CDK9 T-loop at position Thr186, dissociate positive transcription elongation factor b (P-TEFb) from BRD4, and promote the Tat-mediated HIV-1 transcription and RNA polymerase II (RNAPII) C-terminal domain (CTD) on Ser (CTD-Ser2P) to bind to the HIV-1 promoter. This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.
MeSH term(s)	Cell Survival/drug effects ; Cell Survival/physiology ; Dose-Response Relationship, Drug ; HIV-1/drug effects ; HIV-1/metabolism ; Humans ; Jurkat Cells ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Positive Transcriptional Elongation Factor B/metabolism ; Resveratrol/analogs & derivatives ; Resveratrol/pharmacology
Chemical Substances	Positive Transcriptional Elongation Factor B (EC 2.7.11.-) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2021-12-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2021.114901
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