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      Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus

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          Abstract

          Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC 50 of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses.

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          Most cited references42

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          The WHO dengue classification and case definitions: time for a reassessment.

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            Scorpion venom components as potential candidates for drug development

            Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.
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              Resistance to direct antiviral agents in patients with hepatitis C virus infection.

              Chronic hepatitis C virus (HCV) infection is one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure that leads to transplantation. The current standard treatment, a combination of pegylated interferon alfa and ribavirin, eradicates the virus in only about 50% of patients. Directly acting antiviral (DAA) agents, which inhibit HCV replication, are in phase 1, 2, and 3 trials; these include reagents that target the nonstructural (NS)3 protease, the NS5A protein, the RNA-dependent RNA-polymerase NS5B, as well as compounds that directly inhibit HCV replication through interaction with host cell proteins. Because of the high genetic heterogeneity of HCV and its rapid replication, monotherapy with DAA agents poses a high risk for selection of resistant variants. We review the parameters that determine resistance, genotypic and phenotypic resistance profiles of DAA agents, and strategies to avoid the selection of resistant variants.
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                Author and article information

                Contributors
                elbitar@azhar.edu.eg
                msarhan@azhar.edu.eg
                mohamed_hassanain@science.suez.edu.eg
                vquinterohe@conacyt.mx
                nu_chie@people.kobe-u.ac.jp
                mohsenamoustafa@azhar.edu.eg
                possani@ibt.unam.mx
                hotta@kobe-u.ac.jp
                Journal
                Int J Pept Res Ther
                Int J Pept Res Ther
                International Journal of Peptide Research and Therapeutics
                Springer Netherlands (Dordrecht )
                1573-3149
                1573-3904
                6 July 2019
                2020
                : 26
                : 2
                : 811-821
                Affiliations
                [1 ]GRID grid.411303.4, ISNI 0000 0001 2155 6022, Zoology Department, Faculty of Science, , Al-Azhar University, ; Assiut, Egypt
                [2 ]GRID grid.31432.37, ISNI 0000 0001 1092 3077, Department of Microbiology, , Kobe University Graduate School of Medicine, ; 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan
                [3 ]GRID grid.31432.37, ISNI 0000 0001 1092 3077, Department of International Health, , Kobe University Graduate School of Health Sciences, ; 7-10-2 Tomogaoka, Suma-ku, Kobe, 654-0142 Japan
                [4 ]GRID grid.33003.33, ISNI 0000 0000 9889 5690, Zoology Department, Faculty of Science, , Suez Canal University, ; Ismailia, 41522 Egypt
                [5 ]GRID grid.9486.3, ISNI 0000 0001 2159 0001, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, , Universidad Nacional Autónoma de México, ; Avenida Universidad, 2001, Colonia Chamilpa, Apartado Postal 510-3, 62210 Cuernavaca, Morelos Mexico
                [6 ]GRID grid.411659.e, ISNI 0000 0001 2112 2750, CONACYT-Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas-Instituto de Ciencias, , Benemérita Universidad Autónoma de Puebla, ; Ciudad Universitaria, C.P. 72570 Puebla, Mexico
                Author information
                http://orcid.org/0000-0003-0698-8438
                Article
                9888
                10.1007/s10989-019-09888-2
                7223391
                32435168
                526318a9-bc84-4dfb-b143-af21c8c2face
                © Springer Nature B.V. 2019

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 2 July 2019
                Categories
                Article
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                © Springer Nature B.V. 2020

                Biochemistry
                animal venom,antiviral peptide,denv,hcv,scorpio maurus palmatus,smp76
                Biochemistry
                animal venom, antiviral peptide, denv, hcv, scorpio maurus palmatus, smp76

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