HIV entry inhibitors and their potential in HIV therapy

Qian, Keduo; Morris‐Natschke, Susan L.; Lee, Kuo Hsiung̀

doi:10.1002/med.20138

Cited by 109 publications

(102 citation statements)

References 134 publications

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“…An additional anti-HIV drug class is represented by maturation inhibitors (MIs), which, however, are still under clinical development. ART refers to the use of a combination of three or more antiretroviral drugs to treat HIV infection and achieve viral suppression [98-100]; this acronym has substantially replaced the terms of combined ART (cART) and the former HAART abbreviation. In this review, the term HAART will be used only when explicitly referred to in the cited reference.…”

Section: Effect Of Art On Immunosenescence: Friend or Foe?mentioning

confidence: 99%

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Franzese¹,

Barbaccia²,

Bonmassar³

et al. 2018

Chemotherapy

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Since the introduction of highly active antiretroviral therapy more than 2 decades ago, HIV-related deaths have dramatically decreased and HIV infection has become a chronic disease. Due to the inability of antiretroviral drugs to eradicate the virus, treatment of HIV infection requires a systemic lifelong therapy. However, even when successfully treated, HIV patients still show increased incidence of age-associated co-morbidities compared with uninfected individuals. Virus- induced immunosenescence, a process characterized by a progressive decline of immune system function, contributes to the premature ageing observed in HIV patients. Although antiretroviral therapy has significantly improved both the quality and length of patient lives, the life expectancy of treated patients is still shorter compared with that of uninfected individuals. In particular, while antiretroviral therapy can contrast some features of HIV-associated immunosenescence, several anti-HIV agents may themselves contribute to other aspects of immune ageing. Moreover, older HIV patients tend to have a worse immunological response to the antiviral therapy. In this review we will examine the available evidence on the role of antiretroviral therapy in the control of the main features regulating immunosenescence.

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Section: Effect Of Art On Immunosenescence: Friend or Foe?mentioning

confidence: 99%

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Franzese¹,

Barbaccia²,

Bonmassar³

et al. 2018

Chemotherapy

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“…HIV-1 fusion inhibitors [9,10]; HIV-1 entry inhibitors [11,12]; and HIV-1 integrase strand transfer inhibitors [13][14][15]. These drugs target different steps of HIV-1 life cycle.…”

Section: Hiv-1 High-throughput Screening Inhibitor Virus-cell-basementioning

confidence: 99%

Establishment of a high-throughput screening system for universal anti-HIV targets

et al. 2010

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The process of identifying novel human immunodeficiency virus 1 (HIV-1) inhibitors presents a challenge for industrial and scientific research. Virus-cell-based screening approaches offer some advantages in the quest for novel inhibitors because they include multiple targets in a single screen and in some cases reveal targets not captured in biochemical assays. In this study, a high-throughput screening (HTS) system for HIV-1 inhibitors was developed, which allows the simultaneous screening of all the HIV-1 targets required for replication in the cell culture. HeLa/cluster of differentiation 4 (CD4)/long terminal repeat (LTR) indicator cells, which stably expressed high levels of HIV receptor CD4 and contained the firefly luciferase reporter gene under the control of the HIV-1 LTR promoter, were generated. The expression of CD4 and LTR function in this cell line was validated by Western blot and luciferase assay. MT2 cells, a human T-cell leukemia cell line that support high levels of HIV-1 replication, were infected with HIV-1, and then the infected MT2 cells were co-cultured with HeLa/CD4/LTR cells. In the optimized assay conditions, HIV-1 replication occurs rapidly in the MT2 cells, resulting in the infection of the HeLa/CD4/LTR cells and a significant induction of luciferase signals through LTR, which is activated by the expression of HIV-1 tat gene. The luciferase signals of HeLa/CD4/LTR cells co-cultured with HIV-1 infected MT2 cells were significantly stronger than the signals of noninfected HeLa/CD4/LTR cells (P < 0.001). The inhibitory effects of HIV-1 inhibitors (3′-Azido-3′-deoxythymidine [AZT], efavirenz [EFV], and nevirapine [NVP]) were evaluated with this assay, and the inhibitory concentration 50% (IC 50 ) values of the above three inhibitors were 58, 1.4, and 85 nmol/L, respectively, indicating that the assay provides the necessary sensitivity for identifying antiviral molecules. The Z' factor had a value of 0.563, indicating this is a very robust assay. These results suggested that HIV-1 infection assay represents a novel approach to HIV-1 antiviral screening that allows for the effective execution of HTS campaigns. HIV-1, high-throughput screening, inhibitor, virus-cell-based assayCitation: Yin Q, Zhuang D M, Jiang Y Q, et al. Establishment of a high-throughput screening system for universal anti-HIV targets. Chinese Sci Bull, 2010, 55: 937−942,

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“…Since HIV-1's surface proteins, exterior-gp120 and transmembrane-gp41, naturally attach themselves to the negatively charged proteoglycans on the host cell surface, such soluble polyanions as heparin are capable of blocking virion attachment (Qian et al 2009). Moreover, selectivity in the interaction of immobilized heparin with hepatitis B and C viruses, as compared to plasma proteins, was established (Zahn and Allain 2005).…”

Section: Introductionmentioning

confidence: 99%

Removing human immunodeficiency virus (HIV) from human blood using immobilized heparin

et al. 2011

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We report herein that heparin covalently attached to a water-insoluble resin suspended in HIV-infected aqueous buffer or whole blood captures the virus; subsequent physical separation of the immobilized heparin reduced the viral titers by over 80% and 50%, respectively. The detoxification concept has been validated by both circulating an HIV-1 solution through a column packed with the heparin-Sepharose beads and successively mixing an HIV-1 solution with fresh beads.

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HIV entry inhibitors and their potential in HIV therapy

Cited by 109 publications

References 134 publications

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Establishment of a high-throughput screening system for universal anti-HIV targets

Removing human immunodeficiency virus (HIV) from human blood using immobilized heparin

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