An Organic CD4 Inhibitor Reduces the Clinical and Pathological Symptoms of Acute Experimental Allergic Encephalomyelitis

Edling, Andrea E.; Choksi, Swati; Huang, Ziwei; Korngold, Robert

doi:10.1006/jaut.2001.0576

Cited by 16 publications

(4 citation statements)

References 45 publications

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“…However, therapies that block interaction between HIV-1 and CD-4 without impinging on CD4 function, such as the non-immunosuppressive TNX-355 antibody, may prove useful in blocking viral entry. In addition, transient inhibition of CD4 has proven useful in a number of autoimmune diseases, 67,68 and could similarly be used as a short-term adjuvant, for example during activation and clearance of latently infected CD4 + T-cells.…”

Section: Ccr5 Disruption and Other Anti-hiv Entry Therapiesmentioning

confidence: 99%

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART

et al. 2013

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The “Berlin Patient,” who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV+ patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have recently been explored, including disruption of the CCR5 and CXCR4 coreceptor loci in CD4+ T-cells and CD34+ hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as nonhuman primates. Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors, and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells, and emphasize the need to target viral replication pre- and post-entry in order to mount a suitably robust defense against spreading infection.

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Section: Ccr5 Disruption and Other Anti-hiv Entry Therapiesmentioning

confidence: 99%

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART

et al. 2013

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“…Discovery and development of gp120−CD4 binding inhibitors have been objectives of research for a number of researchers, and some interesting gp120−CD4 binding inhibitors have been reported in the literature. ,− Different inhibitors may bind to the different protein sites, particularly different sites of CD4. Some interesting inhibitors were isolated from natural products.…”

Section: Introductionmentioning

confidence: 99%

How Can (−)-Epigallocatechin Gallate from Green Tea Prevent HIV-1 Infection? Mechanistic Insights from Computational Modeling and the Implication for Rational Design of Anti-HIV-1 Entry Inhibitors

Hamza

Chen

2006

J. Phys. Chem. B

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Possible inhibitors preventing human immunodeficiency virus type 1 (HIV-1) entry into the cells are recognized as hopeful next-generation anti-HIV-1 drugs. It is highly desirable to develop a potent inhibitor blocking binding of glycoprotein CD4 of the cell with glycoprotein gp120 of HIV-1, because the gp120-CD4 binding is the initial step of HIV-1 entry into the cells. It has been recently reported that (-)-epigallocatechin gallate (EGCG) from green tea is an inhibitor blocking gp120-CD4 binding. But the inhibitory mechanism remains unknown. For understanding the inhibitory mechanism, extensive molecular docking, molecular dynamics simulations, and binding free-energy calculations have been performed in this study to predict the most favorable structures of CD4-EGCG, gp120-CD4, and gp120-CD4-EGCG binding complexes in water. The results reveal that EGCG binds with CD4 in such a way that the calculated binding affinity of gp120 with the CD4-EGCG complex is negligible. So, the favorable binding of EGCG with CD4 can effectively block gp120-CD4 binding. The calculated CD4-EGCG binding affinity (DeltaG(bind) = -5.5 kcal/mol, K(d) = 94 microM) is in excellent agreement with available experimental data suggesting IC(50) approximately 100 microM for EGCG-blocking CD4-gp120 binding. These results and insights provide a rational basis for future design of novel, more potent inhibitors to block gp120-CD4 binding.

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“…Interestingly, CD4 inhibitors reduced the severity of EAE symptoms in mice. 83 These findings indicated that LA could effectively decrease the invasion of peripheral immune cells and the inflammatory response in the CNS.…”

Section: Discussionmentioning

confidence: 90%

Role of lipoic acid in multiple sclerosis

et al. 2021

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Multiple sclerosis (MS) is a disabling autoimmune disease of the central nervous system (CNS) characterized by demyelination and neurodegeneration. 1 It affects approximately 2.5 million people worldwide and poses a growing burden to society. 2,3 Relapsing-remitting MS (RRMS) is the most common initial course featuring alternate relapse and remission, and disability is aggravated gradually with illness development. 4 After approximately 20 years, around 90% of RRMS patients will develop secondary progressive MS (SPMS) characterized by progressive neurodegeneration without any definite remission periods. 5,6 In addition to SPMS, progressive MS (PMS) also includes

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An Organic CD4 Inhibitor Reduces the Clinical and Pathological Symptoms of Acute Experimental Allergic Encephalomyelitis

Cited by 16 publications

References 45 publications

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART

Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART

How Can (−)-Epigallocatechin Gallate from Green Tea Prevent HIV-1 Infection? Mechanistic Insights from Computational Modeling and the Implication for Rational Design of Anti-HIV-1 Entry Inhibitors

Role of lipoic acid in multiple sclerosis

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