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      Carnosine exhibits significant antiviral activity against Dengue and Zika virus.

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          Abstract

          Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted to humans by their common vector, Aedes mosquitoes. DENV infection represents one of the most widely spread mosquito-borne diseases whereas ZIKV infection occasionally re-emerged in the past causing outbreaks. Although there have been considerable advances in understanding the pathophysiology of these viruses, no effective vaccines or antiviral drugs are currently available. In this study, we evaluated the antiviral activity of carnosine, an endogenous dipeptide (β-alanyl-l-histidine), against DENV serotype 2 (DENV2) and ZIKV infection in human liver cells (Huh7). Computational studies were performed to predict the potential interactions between carnosine and viral proteins. Biochemical and cell-based assays were performed to validate the computational results. Mode-of-inhibition, plaque reduction, and immunostaining assays were performed to determine the antiviral activity of carnosine. Exogenous carnosine showed minimal cytotoxicity in Huh7 cells and rescued the viability of infected cells with EC50 values of 52.3 and 59.5 μM for DENV2 and ZIKV infection, respectively. Based on the mode-of-inhibition assays, carnosine inhibited DENV2 mainly by inhibiting viral genome replication and interfering with virus entry. Carnosine antiviral activity was verified with immunostaining assay where carnosine treatment diminished viral fluorescence signal. In conclusion, carnosine exhibited significant inhibitory effects against DENV2 and ZIKV replication in human liver cells and could be utilized as a lead peptide for the development of effective and safe antiviral agents against DENV and ZIKV.

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          Author and article information

          Journal
          J Pept Sci
          Journal of peptide science : an official publication of the European Peptide Society
          Wiley
          1099-1387
          1075-2617
          Aug 2019
          : 25
          : 8
          Affiliations
          [1 ] Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA, USA.
          [2 ] Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
          [3 ] Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
          Article
          10.1002/psc.3196
          31290226
          cc8b9de3-f106-41c8-ab88-b0adeea0bb47
          © 2019 European Peptide Society and John Wiley & Sons, Ltd.
          History

          NS2B-NS3 protease,Zika virus,antiviral activity,carnosine,dengue virus,dipeptide

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