Cargando…

Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes high mortality rates in humans and it is the most clinically important and common cause of viral encephalitis in Asia. To date, there is no specific treatment for JEV infection. Melatonin, a neurotropic hormone, is reported to be...

Descripción completa

Detalles Bibliográficos
Autores principales: Kitidee, Kuntida, Samutpong, Arisara, Pakpian, Nattaporn, Wisitponchai, Tanchanok, Govitrapong, Piyarat, Reiter, Russel J., Wongchitrat, Prapimpun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099015/
https://www.ncbi.nlm.nih.gov/pubmed/37055489
http://dx.doi.org/10.1038/s41598-023-33254-4
_version_ 1785024955449081856
author Kitidee, Kuntida
Samutpong, Arisara
Pakpian, Nattaporn
Wisitponchai, Tanchanok
Govitrapong, Piyarat
Reiter, Russel J.
Wongchitrat, Prapimpun
author_facet Kitidee, Kuntida
Samutpong, Arisara
Pakpian, Nattaporn
Wisitponchai, Tanchanok
Govitrapong, Piyarat
Reiter, Russel J.
Wongchitrat, Prapimpun
author_sort Kitidee, Kuntida
collection PubMed
description Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes high mortality rates in humans and it is the most clinically important and common cause of viral encephalitis in Asia. To date, there is no specific treatment for JEV infection. Melatonin, a neurotropic hormone, is reported to be effective in combating various bacterial and viral infections. However, the effects of melatonin on JEV infection have not yet been studied. The investigation tested the antiviral effects of melatonin against JEV infection and elucidated the possible molecular mechanisms of inhibition. Melatonin inhibited the viral production in JEV-infected SH-SY5Y cells in a time- and dose-dependent manner. Time-of-addition assays demonstrated a potent inhibitory effect of melatonin at the post-entry stage of viral replication. Molecular docking analysis revealed that melatonin negatively affected viral replication by interfering with physiological function and/or enzymatic activity of both JEV nonstructural 3 (NS3) and NS5 protein, suggesting a possible underlying mechanism of JEV replication inhibition. Moreover, treatment with melatonin reduced neuronal apoptosis and inhibited neuroinflammation induced by JEV infection. The present findings reveal a new property of melatonin as a potential molecule for the further development of anti-JEV agents and treatment of JEV infection.
format Online
Article
Text
id pubmed-10099015
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-100990152023-04-14 Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells Kitidee, Kuntida Samutpong, Arisara Pakpian, Nattaporn Wisitponchai, Tanchanok Govitrapong, Piyarat Reiter, Russel J. Wongchitrat, Prapimpun Sci Rep Article Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes high mortality rates in humans and it is the most clinically important and common cause of viral encephalitis in Asia. To date, there is no specific treatment for JEV infection. Melatonin, a neurotropic hormone, is reported to be effective in combating various bacterial and viral infections. However, the effects of melatonin on JEV infection have not yet been studied. The investigation tested the antiviral effects of melatonin against JEV infection and elucidated the possible molecular mechanisms of inhibition. Melatonin inhibited the viral production in JEV-infected SH-SY5Y cells in a time- and dose-dependent manner. Time-of-addition assays demonstrated a potent inhibitory effect of melatonin at the post-entry stage of viral replication. Molecular docking analysis revealed that melatonin negatively affected viral replication by interfering with physiological function and/or enzymatic activity of both JEV nonstructural 3 (NS3) and NS5 protein, suggesting a possible underlying mechanism of JEV replication inhibition. Moreover, treatment with melatonin reduced neuronal apoptosis and inhibited neuroinflammation induced by JEV infection. The present findings reveal a new property of melatonin as a potential molecule for the further development of anti-JEV agents and treatment of JEV infection. Nature Publishing Group UK 2023-04-13 /pmc/articles/PMC10099015/ /pubmed/37055489 http://dx.doi.org/10.1038/s41598-023-33254-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kitidee, Kuntida
Samutpong, Arisara
Pakpian, Nattaporn
Wisitponchai, Tanchanok
Govitrapong, Piyarat
Reiter, Russel J.
Wongchitrat, Prapimpun
Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title_full Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title_fullStr Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title_full_unstemmed Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title_short Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells
title_sort antiviral effect of melatonin on japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in sh-sy5y cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099015/
https://www.ncbi.nlm.nih.gov/pubmed/37055489
http://dx.doi.org/10.1038/s41598-023-33254-4
work_keys_str_mv AT kitideekuntida antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT samutpongarisara antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT pakpiannattaporn antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT wisitponchaitanchanok antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT govitrapongpiyarat antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT reiterrusselj antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells
AT wongchitratprapimpun antiviraleffectofmelatoninonjapaneseencephalitisvirusinfectioninvolvesinhibitionofneuronalapoptosisandneuroinflammationinshsy5ycells