Antiviral Activity and Metabolism of the Castanospermine Derivative MDL 28,574, in Cells Infected with Herpes Simplex Virus Type 2

Ahmed, Sohail; Nash, Robert J.; Bridges, C G; Taylor, Debra L.; Kang, M.S.; Porter, Elaine A.; Tyms, A. S.

doi:10.1006/bbrc.1995.1333

Cited by 27 publications

(11 citation statements)

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“…2B), there is a strong potential benefit of using inhibitors of MOGS as a means of controlling viral infections, especially those that pose a threat of rapid global spreading. Previous in vitro studies have shown that MOGS inhibitors such as castanospermine, N -butyldeoxynojirimycin (miglustat; previously known as NB-DNJ), or deoxynojirimycin can reduce viral replication in HIV infection, dengue, herpes simplex virus type 2 infection, and hepatitis C. 17-20 In a clinical study, patients with HIV-1 infection who received a combination of NB-DNJ and zidovudine had lower plasma viremia and higher CD4+ T-cell counts throughout the study than did patients who received zidovudine alone. 21 The side effects of combination therapy were not severe and included flatulence, diarrhea, paresthesias, and mild decreases in the hemoglobin level and platelet and neutrophil counts, as compared with treatment with zidovudine alone.…”

Section: Discussionmentioning

confidence: 99%

Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Sadat¹,

Moir²,

Chun³

et al. 2014

N Engl J Med

120

114

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Summary Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.

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Section: Discussionmentioning

confidence: 99%

Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Sadat¹,

Moir²,

Chun³

et al. 2014

N Engl J Med

120

114

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“…In both lectin and protein-based glycoprotein recognition, the glycan structure is critical to successful infection, as demonstrated in patients with CDG- MOGS (30). Several MOGS inhibitors have been developed, and have demonstrated the ability to reduce viral entry, replication, and virulence in vitro (70–72). In a clinical trial, patients treated with the MOGS inhibitor miglustat in combination with zidovudine had lower plasma viral loads and higher CD4 + T cell counts compared to those treated with zidovudine alone, without significant side effects (73).…”

Section: Therapeutic Manipulation Of Glycansmentioning

confidence: 99%

Glycans Instructing Immunity: The Emerging Role of Altered Glycosylation in Clinical Immunology

2015

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Protein glycosylation is an important epigenetic modifying process affecting expression, localization, and function of numerous proteins required for normal immune function. Recessive germline mutations in genes responsible for protein glycosylation processes result in congenital disorders of glycosylation and can have profound immunologic consequences. Genetic mutations in immune signaling pathways that affect glycosylation sites have also been shown to cause disease. Sugar supplementation and in vivo alteration of glycans by medication holds therapeutic promise for some of these disorders. Further understanding of how changes in glycosylation alter immunity may provide novel treatment approaches for allergic disease, immune dysregulation, and immunodeficiency in the future.

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“…CST, its derivative celgosivir (6 O-butanoyl castanospermine) and DNJ have been described to inhibit the replication of multiple viruses both in vitro and in vivo [117][118][119][187][188][189][190][191][192][193][194][195][196][197] (Table 2). In mammalian cells both compounds block the function of ER α-glucosidases I and II.…”

Section: Bsas Derived From Plants: Castanospermine 1-deoxynojirimycimentioning

confidence: 99%

“…Still, whether CV-N has a binding partner in the host has not been determined yet and further studies are needed to assess the safety of CV-N as a therapeutic drug. HSV-2 EC50 < 4µM in plaque assay 190,191 HIV 100 µg/mL 100% syncitia inhibition in H9 and CD4-Jurkat cells 188,199,229,230 Lantibiotics are peptides with unusual amino acids produced by several gram-positive bacteria 249,250 . Labyrinthopeptin A1 (LabyA1) (16) belongs to a novel class of carbacyclic lantibiotics 251 , 252 that was isolated from the actinomycete Actinomadura namibiensis.…”

Section: Bsas Derived From Plants: Castanospermine 1-deoxynojirimycimentioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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, but cannot be converted to PDF. You must view these files (e.g. movies) online.Scheme 1_(structures 1-5)_named.cdx Scheme 2_(structures 6-8)_named.cdx Scheme 3_(structure 9)_named.cdx Scheme 4_(structure 10)_named.cdx Scheme 5_ (structures 11-12) The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with skepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has rebloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, taking particular focus on natural products as promising starting points for antiviral lead development.

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Antiviral Activity and Metabolism of the Castanospermine Derivative MDL 28,574, in Cells Infected with Herpes Simplex Virus Type 2

Cited by 27 publications

References 0 publications

Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections

Glycans Instructing Immunity: The Emerging Role of Altered Glycosylation in Clinical Immunology

Antiviral drug discovery: broad-spectrum drugs from nature

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