{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:06:59Z","timestamp":1792058819575,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FRGS grant: FP007\u20102017A"],"award-info":[{"award-number":["FRGS grant: FP007\u20102017A"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses transmitted to humans by their common vector, <jats:italic>Aedes<\/jats:italic> mosquitoes. DENV infection represents one of the most widely spread mosquito\u2010borne diseases whereas ZIKV infection occasionally re\u2010emerged 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 (\u03b2\u2010alanyl\u2010<jats:sc>l<\/jats:sc>\u2010histidine), 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\u2010based assays were performed to validate the computational results. Mode\u2010of\u2010inhibition, 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 EC<jats:sub>50<\/jats:sub> values of 52.3 and 59.5 \u03bcM for DENV2 and ZIKV infection, respectively. Based on the mode\u2010of\u2010inhibition 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.<\/jats:p>","DOI":"10.1002\/psc.3196","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T03:22:03Z","timestamp":1562728923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Carnosine exhibits significant antiviral activity against Dengue and Zika virus"],"prefix":"10.1002","volume":"25","author":[{"given":"Hussin A.","family":"Rothan","sequence":"first","affiliation":[{"name":"Department of Biology, College of Arts and Sciences Georgia State University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar Yasir","family":"Abdulrahman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8830-441X","authenticated-orcid":false,"given":"Ahmad Suhail","family":"Khazali","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurshamimi","family":"Nor Rashid","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teoh Teow","family":"Chong","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohana","family":"Yusof","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine University of Malaya  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO.Dengue vaccine: WHO position paper\u2014September 2018. 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