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Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many...

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Autores principales: Chen, Han-Hsiang, Lin, Chin-Jung, Anand, Anisha, Lin, Han-Jia, Lin, Hung-Yun, Mao, Ju-Yi, Wang, Pei-Hua, Tseng, Yufeng Jane, Tzou, Wen-Shyong, Huang, Chih-Ching, Wang, Robert Y.L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123278/
https://www.ncbi.nlm.nih.gov/pubmed/35452675
http://dx.doi.org/10.1016/j.jbc.2022.101957
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author Chen, Han-Hsiang
Lin, Chin-Jung
Anand, Anisha
Lin, Han-Jia
Lin, Hung-Yun
Mao, Ju-Yi
Wang, Pei-Hua
Tseng, Yufeng Jane
Tzou, Wen-Shyong
Huang, Chih-Ching
Wang, Robert Y.L.
author_facet Chen, Han-Hsiang
Lin, Chin-Jung
Anand, Anisha
Lin, Han-Jia
Lin, Hung-Yun
Mao, Ju-Yi
Wang, Pei-Hua
Tseng, Yufeng Jane
Tzou, Wen-Shyong
Huang, Chih-Ching
Wang, Robert Y.L.
author_sort Chen, Han-Hsiang
collection PubMed
description Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.
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spelling pubmed-91232782022-05-24 Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein Chen, Han-Hsiang Lin, Chin-Jung Anand, Anisha Lin, Han-Jia Lin, Hung-Yun Mao, Ju-Yi Wang, Pei-Hua Tseng, Yufeng Jane Tzou, Wen-Shyong Huang, Chih-Ching Wang, Robert Y.L. J Biol Chem Research Article Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections. American Society for Biochemistry and Molecular Biology 2022-04-20 /pmc/articles/PMC9123278/ /pubmed/35452675 http://dx.doi.org/10.1016/j.jbc.2022.101957 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Chen, Han-Hsiang
Lin, Chin-Jung
Anand, Anisha
Lin, Han-Jia
Lin, Hung-Yun
Mao, Ju-Yi
Wang, Pei-Hua
Tseng, Yufeng Jane
Tzou, Wen-Shyong
Huang, Chih-Ching
Wang, Robert Y.L.
Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title_full Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title_fullStr Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title_full_unstemmed Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title_short Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein
title_sort development of antiviral carbon quantum dots that target the japanese encephalitis virus envelope protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123278/
https://www.ncbi.nlm.nih.gov/pubmed/35452675
http://dx.doi.org/10.1016/j.jbc.2022.101957
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