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      Natural Products as Source of Potential Dengue Antivirals

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          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.

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          Most cited references48

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          Dengue/dengue hemorrhagic fever: the emergence of a global health problem.

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            Association between nasal shedding and fever that influenza A (H3N2) induces in dogs

            Background Avian origin canine influenza virus was reported in Korea. The dog to dog contact transmission of the avian origin canine influenza virus (CIV) H3N2 and CIV H3N8 was shown by experimental contact transmission. This study was focused on viral excretion and fever in order to elucidate the epidemiological associations which might be helpful to control the disease transmissions in CIV outbreak in dogs. Methods An influenza seronegative 10-week-old Beagle dog was experimentally inoculated with the canine influenza virus A/canine/01/2007, subtype H3N2. Eight hours after inoculation, the infected dog was cohoused with seven uninfected Beagle dogs. Clinical signs including fever were recorded for 14 days post inoculation. Results The infected dog and four of seven contact dogs in the study showed clinical signs (sneezing, nasal discharge and coughing) during the study. Viral shedding occurred in all of the animals tested and began on 1 to 6 DPI in dogs with clinical signs. Elevated body temperatures above 39.5°C (geometric mean temperature of 39.86°C±0.49) were observed in all symptomatic dogs. The mean viral titer during fever was 2.99 log EID50/ml, which was significantly higher than the viral titer detected in the non fever. Conclusions The data show that contact dogs with a canine influenza infected dog shed different levels of virus in their nasal excretions and demonstrate that clinical signs, including fever, significantly correlate with the viral shedding.
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              Therapies from Fucoidan; Multifunctional Marine Polymers

              Published research on fucoidans increased three fold between 2000 and 2010. These algal derived marine carbohydrate polymers present numerous valuable bioactivities. This review discusses the role for fucoidan in the control of acute and chronic inflammation via selectin blockade, enzyme inhibition and inhibiting the complement cascade. The recent data on toxicology and uptake of fucoidan is detailed together with a discussion on the comparative activities of fractions of fucoidan from different sources. Recent in vivo, in vitro and clinical research related to diverse clinical needs is discussed. Targets include osteoarthritis, kidney and liver disease, neglected infectious diseases, hemopoietic stem cell modulation, protection from radiation damage and treatments for snake envenomation. In recent years, the production of well characterized reproducible fucoidan fractions on a commercial scale has become possible making therapies from fucoidan a realizable goal.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                17 June 2014
                June 2014
                : 19
                : 6
                : 8151-8176
                Affiliations
                [1 ]Departamento de Química, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                [2 ]Instituto Federal de Educação, Ciência e Tecnologia do Norte de Minas, 39900-000 Almenara, MG, Brazil
                [3 ]Departamento de Microbiologia, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                [4 ]Departamento de Biologia Geral, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil
                Author notes
                [* ]Authors to whom correspondence should be addressed: E-MailS: robsonr.teixeira@ 123456ufv.br (R.R.T.); depaula@ 123456ufv.br (S.O.P.); Tel.: +55-31-3899-3209 (R.R.T.); +55-31-3899-2589 (S.O.P.); Fax: +55-31-3899-2370 (R.R.T.); +55-31-3899-2549 (S.O.P.).
                Article
                molecules-19-08151
                10.3390/molecules19068151
                6271820
                24941340
                6772534a-86b8-4f90-9459-96487ede6dfd
                © 2014 by the authors.

                licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 14 March 2014
                : 04 June 2014
                : 05 June 2014
                Categories
                Review

                dengue virus,dengue fever,antiviral natural products

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