Crabohydrate-Related Inhibitors of Dengue Virus Entry

Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, and Global COE Program for Innovation in Human Health Sciences, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan. .
Viruses (Impact Factor: 3.28). 02/2013; 5(2):605-18. DOI: 10.3390/v5020605
Source: PubMed

ABSTRACT Dengue virus (DENV), which is transmitted by Aedes mosquitoes, causes fever and hemorrhagic disorders in humans. The virus entry process mediated through host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue disease. Therefore, elucidation of the molecular mechanisms underlying virus entry is essential for an understanding of dengue pathology and for the development of effective new anti-dengue agents. DENV binds to its receptor molecules mediated through a viral envelope (E) protein, followed by incorporation of the virus-receptor complex inside cells. The fusion between incorporated virus particles and host endosome membrane under acidic conditions is mediated through the function of DENV E protein. Carbohydrate molecules, such as sulfated glycosaminoglycans (GAG) and glycosphingolipids, and carbohydrate-recognition proteins, termed lectins, inhibit virus entry. This review focuses on carbohydrate-derived entry inhibitors, and also introduces functionally related compounds with similar inhibitory mechanisms against DENV entry.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dengue is a neglected disease responsible for 22,000 deaths each year in areas where it is endemic. To date, there is no clinically approved dengue vaccine or antiviral for human beings, even though there have been great efforts to accomplish these goals. Several approaches have been used in the search for dengue antivirals such as screening of compounds against dengue virus enzymes and structure-based computational discovery. During the last decades, researchers have turned their attention to nature, trying to identify compounds that can be used as dengue antivirals. Nature represents a vast reservoir of substances that can be explored with the aim of discovering new leads that can be either used directly as pharmaceuticals or can serve as lead structures that can be optimized towards the development of new antiviral agents against dengue. In this review we describe an assortment of natural products that have been reported as possessing dengue antiviral activity. The natural products are organized into classes of substances. When appropriate, structure-activity relationships are outlined. The biological assays used to assess antiviral activity are briefly described.
    Molecules 06/2014; DOI:10.3390/molecules19068151 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review considers a plethora of multidisciplinary literature relating to seaweeds and their bioactive metabolites. Rather than providing another stocktake of the diverse metabolites and applications, we undertake a meta-analysis of the status and direction of research and development towards biological applications. Of significance is that for health and medical applications specifically, the dominant focus remains on the unique and abundant sulfated polysaccharides. However, there is a shift from the historical publications that emerged during the development of the hydrocolloid industry in the last century. Recent development focuses on the huge diversity of these metabolites across more species and at finer structural scale. This is concurrent with the frontier of research in glycobiology where sulfated polysaccharide macromolecules are shown to have specific and important biological activities related to key molecular traits. Phycologists, biochemists, chemical engineers and health and medical researchers will build the teams that can deliver production and consistency of these complex molecules.
    Advances in Botanical Research - Sea Plants, Sea Plants edited by Nathalie Bourgounon, 05/2014: chapter Controlling seaweed biology, physiology and metabolic traits in production for commercially relevant bio-actives in glycobiology: pages 221-252; Elsevier., ISBN: ISSN 0065-2296
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most animal species exhibit sexually dimorphic behaviors, many of which are linked to reproduction. A number of these behaviors, including blood feeding in female mosquitoes, contribute to the global spread of vector-borne illnesses. However, knowledge concerning the genetic basis of sexually dimorphic traits is limited in any organism, including mosquitoes, especially with respect to differences in the developing nervous system. Custom microarrays were used to examine global differences in female vs. male gene expression in the developing pupal head of the dengue vector mosquito, Aedes aegypti. The spatial expression patterns of a subset of differentially expressed transcripts were examined in the developing female vs. male pupal brain through in situ hybridization experiments. Small interfering RNA (siRNA)-mediated knockdown studies were used to assess the putative role of Doublesex, a terminal component of the sex determination pathway, in the regulation of sex-specific gene expression observed in the developing pupal brain. Transcripts (2,527), many of which were linked to proteolysis, the proteasome, metabolism, catabolic, and biosynthetic processes, ion transport, cell growth, and proliferation, were found to be differentially expressed in A. aegypti female vs. male pupal heads. Analysis of the spatial expression patterns for a subset of dimorphically expressed genes in the pupal brain validated the data set and also facilitated the identification of brain regions with dimorphic gene expression. In many cases, dimorphic gene expression localized to the optic lobe. Sex-specific differences in gene expression were also detected in the antennal lobe and mushroom body. siRNA-mediated gene targeting experiments demonstrated that Doublesex, a transcription factor with consensus binding sites located adjacent to many dimorphically expressed transcripts that function in neural development, is required for regulation of sex-specific gene expression in the developing A. aegypti brain. These studies revealed sex-specific gene expression profiles in the developing A. aegypti pupal head and identified Doublesex as a key regulator of sexually dimorphic gene expression during mosquito neural development.
    10/2014; 5:10. DOI:10.1186/s13293-014-0010-x


Available from