Carnosine exhibits significant antiviral activity against Dengue and Zika virus

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...

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Main Authors: Rothan, Hussin A., Abdulrahman, Ammar Yasir, Khazali, Ahmad Suhail, Rashid, Nurshamimi Nor, Teoh, Teow Chong, Yusof, Rohana
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Published: Wiley 2019
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Online Access:http://eprints.um.edu.my/23624/
https://doi.org/10.1002/psc.3196
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spelling my.um.eprints.236242020-01-29T04:27:43Z http://eprints.um.edu.my/23624/ Carnosine exhibits significant antiviral activity against Dengue and Zika virus Rothan, Hussin A. Abdulrahman, Ammar Yasir Khazali, Ahmad Suhail Rashid, Nurshamimi Nor Teoh, Teow Chong Yusof, Rohana QR Microbiology R Medicine 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. Wiley 2019 Article PeerReviewed 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 https://doi.org/10.1002/psc.3196 doi:10.1002/psc.3196
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic QR Microbiology
R Medicine
spellingShingle QR Microbiology
R Medicine
Rothan, Hussin A.
Abdulrahman, Ammar Yasir
Khazali, Ahmad Suhail
Rashid, Nurshamimi Nor
Teoh, Teow Chong
Yusof, Rohana
Carnosine exhibits significant antiviral activity against Dengue and Zika virus
description 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.
format Article
author Rothan, Hussin A.
Abdulrahman, Ammar Yasir
Khazali, Ahmad Suhail
Rashid, Nurshamimi Nor
Teoh, Teow Chong
Yusof, Rohana
author_facet Rothan, Hussin A.
Abdulrahman, Ammar Yasir
Khazali, Ahmad Suhail
Rashid, Nurshamimi Nor
Teoh, Teow Chong
Yusof, Rohana
author_sort Rothan, Hussin A.
title Carnosine exhibits significant antiviral activity against Dengue and Zika virus
title_short Carnosine exhibits significant antiviral activity against Dengue and Zika virus
title_full Carnosine exhibits significant antiviral activity against Dengue and Zika virus
title_fullStr Carnosine exhibits significant antiviral activity against Dengue and Zika virus
title_full_unstemmed Carnosine exhibits significant antiviral activity against Dengue and Zika virus
title_sort carnosine exhibits significant antiviral activity against dengue and zika virus
publisher Wiley
publishDate 2019
url http://eprints.um.edu.my/23624/
https://doi.org/10.1002/psc.3196
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