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Heterogeneity of HIV-1 latent reservoirs

Chinese Medical Journal 2020年第23期133卷 2867-2873页

作者： Jia-Cong Zhao Kai Deng Institute of Human Virology Key Laboratory of Tropical Disease Control of Ministry of EducationZhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Department of Immunology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China

Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent *** order to reduce or eliminate the HIV-1 latent reservoir,characteristics of the latently infected cells need to be intensively studied,and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic ***,we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs,and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome(AIDS).

关键词： Clonal expansion Heterogeneity human immunodeficiency virus-1 HIV-1 Integration sites latent reservoirs

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Discovery of Piperidine-linked Quinazoline Derivatives as Potent HIV-1 NNRTIs and HIV-1 latent Reservoir Activators

Discovery of Piperidine-linked Quinazoline Derivatives as Po...

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作者： Samuel Desta 山东大学

学位级别：硕士

Acquired immune deficiency syndrome（AIDS）,mainly caused by human immunodeficiency virus type-1（HIV-1）,is still one of the leading causes of death *** highly active antiretroviral therapy（HAART）regimens,a combination of three or more HIV-1 antiretroviral targeting different steps of active viral replication,is used as the most efficient treatment regimen in controlling HIV-1 replication in infected ***-nucleoside reverse transcriptase inhibitors（NNRTIs）comprise an important component of HAART,owing to their potent antiviral activity,high selectivity and generally good ***,the efficacy of NNRTIs is compromised by the emergence of drug-resistant mutations,poor pharmacokinetic properties and severe toxic side effects over long-term *** impose the development of new NNRTIs with broader antiviral spectrum and better pharmacokinetic *** induce conformational change of the active site by binding to HIV-1 reverse transcriptase at a site distinct from the DNA polymerase active site of the enzyme,and inhibit retroviral reverse transcription step of HIV-1 replication in a non-competitive *** the past few years,diarylpyrimidine（DAPY）-based NNRTIs,represented by etravirine（ETR）and rilpivirine（RPV）,have attracted considerable attention because of their exceptional characteristics such as positional adaptability and conformational flexibility,which might serve to minimize the loss of binding stabilization caused by *** addition,the key hydrogen bonds and specifically targeting conserved residues of reverse transcriptase provide important avenues for further optimization and development of anti-HIV drug *** thesis has two *** Ⅰ.Design,Synthesis and Biological Evaluation of Piperidine-linked Quinazoline Derivatives as Potent HIV-1 NNRTIsBy employing molecular hybridization and scaffold hopping strategy,the two tolerant regions of non-nucleoside inhibitory binding pocket（NNIBP）were explor

关键词： NNRTIs Quinazoline Drug resistance HIV-1 latent reservoirs LRAs HDACIs

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