Carnosine exhibits significant antiviral activity against Dengue and Zika virus

Rothan, Hussin A. and Abdulrahman, Ammar Yasir and Khazali, Ahmad Suhail and Rashid, Nurshamimi Nor and Teoh, Teow Chong and Yusof, Rohana (2019) Carnosine exhibits significant antiviral activity against Dengue and Zika virus. Journal of Peptide Science, 25 (8). e3196. ISSN 1075-2617, DOI

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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. © 2019 European Peptide Society and John Wiley & Sons, Ltd.

Item Type: Article
Funders: University of Malaya Postgraduate Research Grant (PPP): Research PG012‐2014B, Ministry of Higher Education of Malaysia through FRGS grant: FP007‐2017A
Uncontrolled Keywords: antiviral activity; carnosine; dengue virus; dipeptide; NS2B-NS3 protease; Zika virus
Subjects: Q Science > QR Microbiology
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 29 Jan 2020 04:25
Last Modified: 29 Jan 2020 04:27

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