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      The Signaling Pathways, and Therapeutic Targets of Antiviral Agents: Focusing on the Antiviral Approaches and Clinical Perspectives of Anthocyanins in the Management of Viral Diseases

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          Abstract

          As the leading cause of death worldwide, viruses significantly affect global health. Despite the rapid progress in human healthcare, there are few viricidal and antiviral therapies that are efficient enough. The rapid emergence of resistance, and high costs, as well as the related side effects of synthetic antiviral drugs, raise the need to identify novel, effective, and safe alternatives against viral diseases. Nature has been of the most exceptional help and source of inspiration for developing novel multi-target antiviral compounds, affecting several steps of the viral life cycle and host proteins. For that matter and due to safety and efficacy limitations, as well as high resistance rate of conventional therapies, hundreds of natural molecules are preferred over the synthetic drugs. Besides, natural antiviral agents have shown acceptable antiviral value in both preclinical and clinical trials.This is the first review regarding molecular and cellular pathways of the virus life cycle, treatment strategies, and therapeutic targets of several viral diseases with a particular focus on anthocyanins as promising natural compounds for significant antiviral enhancements. Clinical applications and the need to develop nano-formulation of anthocyanins in drug delivery systems are also considered.

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          Most cited references221

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          Chemical studies of anthocyanins: A review

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            Anthocyanins and their role in cancer prevention.

            Anthocyanins are the most abundant flavonoid constituents of fruits and vegetables. The conjugated bonds in their structures, which absorb light at about 500 nm, are the basis for the bright red, blue and purple colors of fruits and vegetables, as well as the autumn foliage of deciduous trees. The daily intake of anthocyanins in residents of the United States is estimated to be about 200 mg or about 9-fold higher than that of other dietary flavonoids. In this review, we summarize the latest developments on the anti-carcinogenic activities of anthocyanins and anthocyanin-rich extracts in cell culture models and in animal model tumor systems, and discuss their molecular mechanisms of action. We also suggest reasons for the apparent lack of correlation between the effectiveness of anthocyanins in laboratory model systems and in humans as evidenced by epidemiological studies. Future studies aimed at enhancing the absorption of anthocyanins and/or their metabolites are likely to be necessary for their ultimate use for chemoprevention of human cancer.
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              Influenza virus M2 protein has ion channel activity.

              The influenza virus M2 protein was expressed in Xenopus laevis oocytes and shown to have an associated ion channel activity selective for monovalent ions. The anti-influenza virus drug amantadine hydrochloride significantly attenuated the inward current induced by hyperpolarization of oocyte membranes. Mutations in the M2 membrane-spanning domain that confer viral resistance to amantadine produced currents that were resistant to the drug. Analysis of the currents of these altered M2 proteins suggests that the channel pore is formed by the transmembrane domain of the M2 protein. The wild-type M2 channel was found to be regulated by pH. The wild-type M2 ion channel activity is proposed to have a pivotal role in the biology of influenza virus infection.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                08 November 2019
                2019
                : 10
                : 1207
                Affiliations
                [1] 1Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences , Isfahan, Iran
                [2] 2Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences , Kermanshah, Iran
                [3] 3Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences , Isfahan, Iran
                [4] 4Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile , Santiago, Chile
                Author notes

                Edited by: Banasri Hazra, Jadavpur University, India

                Reviewed by: Santhi Gorantla, University of Nebraska Medical Center, United States; Mingze Qin, Shenyang Pharmaceutical University, China

                *Correspondence: Mohammad Hosein Farzaei, mh.farzaei@ 123456gmail.com ; Javier Echeverria, javier.echeverriam@ 123456usach.cl

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.01207
                6856223
                f9805c9a-539f-41ad-80f2-e3242b084feb
                Copyright © 2019 Mohammadi Pour, Fakhri, Asgary, Farzaei and Echeverría

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 July 2019
                : 19 September 2019
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 271, Pages: 23, Words: 11810
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                anthocyanins,natural compounds,antiviral,viral diseases,signaling pathways,therapeutic targets

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