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1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro

BACKGROUND: Enterovirus 71 (EV-71) is a nonenveloped, single-stranded positive-sense RNA virus belonging to genus Enterovius, family Picornaviridae. EV-71 has caused recurrent outbreaks of hand, foot, and mouth disease especially among children in Asia. Some patients develop severe complications, su...

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Autores principales: Chan, Jasper, Tsang, Jessica, Zou, Zijiao, Chik, Kenn, Yuan, Shuofeng, Chu, Hin, Lau, Susanna, Yuen, Kwok-Yung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254896/
http://dx.doi.org/10.1093/ofid/ofy210.1555
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author Chan, Jasper
Tsang, Jessica
Zou, Zijiao
Chik, Kenn
Yuan, Shuofeng
Chu, Hin
Lau, Susanna
Yuen, Kwok-Yung
author_facet Chan, Jasper
Tsang, Jessica
Zou, Zijiao
Chik, Kenn
Yuan, Shuofeng
Chu, Hin
Lau, Susanna
Yuen, Kwok-Yung
author_sort Chan, Jasper
collection PubMed
description BACKGROUND: Enterovirus 71 (EV-71) is a nonenveloped, single-stranded positive-sense RNA virus belonging to genus Enterovius, family Picornaviridae. EV-71 has caused recurrent outbreaks of hand, foot, and mouth disease especially among children in Asia. Some patients develop severe complications, such as meningitis, encephalitis, poliomyelitis-like paralysis, myocarditis, and pulmonary edema. There are currently limited treatment options for EV-71 infection. OSU-03012 is a celecoxib derivative cellular kinase inhibitor with no inhibiting activity on cyclooxygenase that has antiviral activities against a broad-spectrum of viruses, including flaviviruses, filoviruses, and arenaviruses. METHODS: Two clinical isolates of EV-71 obtained from patients with laboratory-confirmed EV-71 infections were included in the study. We evaluated the in vitro anti-EV-71 activity of OSU-03012, using virus yield reduction assays (by quantitative reverse transcription-polymerase chain reaction), cell protection assay, and plaque reduction assay in multiple cell lines. RESULTS: OSU-03012 inhibited both EV-71 strains in U251 (neuronal) and RD (rhabdomyosarcoma) cells. The half maximal inhibitory concentration (IC(50)) of OSU-03012 against EV-71 was consistently <2 µM in these cell lines in the virus yield reduction assay. At 2µM of OSU-03012, there was a nearly 2-log reduction in viral RNA load in both U251 and RD cells. There was a dose-dependent increase in the percentage of viable cells after the addition of 0 to 2 µM of OSU-03012 in EV-71-infected U251 and RD cells in the cell protection assay. In the plaque reduction assay, there was >70% reduction in plaque numbers with the addition of 2 µM of OSU-03012. CONCLUSION: OSU-03012 exhibits anti-EV-71 activity in vitro. The treatment effects of OSU-03012 should be further evaluated in representative animal models of severe EV-71 infection to provide further data for potential clinical evaluation in the future. DISCLOSURES: J. Chan, Pfizer Corporation Hong Kong: Travel grant recipient, Grant recipient. Astellas Pharma Hong Kong Corporation Limited: Travel grant recipient, Grant recipient. Gilead Sciences Hong Kong Limited: Invited speaker, Speaker honorarium. Luminex Corporation: Invited speaker, Speaker honorarium.
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spelling pubmed-62548962018-11-28 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro Chan, Jasper Tsang, Jessica Zou, Zijiao Chik, Kenn Yuan, Shuofeng Chu, Hin Lau, Susanna Yuen, Kwok-Yung Open Forum Infect Dis Abstracts BACKGROUND: Enterovirus 71 (EV-71) is a nonenveloped, single-stranded positive-sense RNA virus belonging to genus Enterovius, family Picornaviridae. EV-71 has caused recurrent outbreaks of hand, foot, and mouth disease especially among children in Asia. Some patients develop severe complications, such as meningitis, encephalitis, poliomyelitis-like paralysis, myocarditis, and pulmonary edema. There are currently limited treatment options for EV-71 infection. OSU-03012 is a celecoxib derivative cellular kinase inhibitor with no inhibiting activity on cyclooxygenase that has antiviral activities against a broad-spectrum of viruses, including flaviviruses, filoviruses, and arenaviruses. METHODS: Two clinical isolates of EV-71 obtained from patients with laboratory-confirmed EV-71 infections were included in the study. We evaluated the in vitro anti-EV-71 activity of OSU-03012, using virus yield reduction assays (by quantitative reverse transcription-polymerase chain reaction), cell protection assay, and plaque reduction assay in multiple cell lines. RESULTS: OSU-03012 inhibited both EV-71 strains in U251 (neuronal) and RD (rhabdomyosarcoma) cells. The half maximal inhibitory concentration (IC(50)) of OSU-03012 against EV-71 was consistently <2 µM in these cell lines in the virus yield reduction assay. At 2µM of OSU-03012, there was a nearly 2-log reduction in viral RNA load in both U251 and RD cells. There was a dose-dependent increase in the percentage of viable cells after the addition of 0 to 2 µM of OSU-03012 in EV-71-infected U251 and RD cells in the cell protection assay. In the plaque reduction assay, there was >70% reduction in plaque numbers with the addition of 2 µM of OSU-03012. CONCLUSION: OSU-03012 exhibits anti-EV-71 activity in vitro. The treatment effects of OSU-03012 should be further evaluated in representative animal models of severe EV-71 infection to provide further data for potential clinical evaluation in the future. DISCLOSURES: J. Chan, Pfizer Corporation Hong Kong: Travel grant recipient, Grant recipient. Astellas Pharma Hong Kong Corporation Limited: Travel grant recipient, Grant recipient. Gilead Sciences Hong Kong Limited: Invited speaker, Speaker honorarium. Luminex Corporation: Invited speaker, Speaker honorarium. Oxford University Press 2018-11-26 /pmc/articles/PMC6254896/ http://dx.doi.org/10.1093/ofid/ofy210.1555 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Chan, Jasper
Tsang, Jessica
Zou, Zijiao
Chik, Kenn
Yuan, Shuofeng
Chu, Hin
Lau, Susanna
Yuen, Kwok-Yung
1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title_full 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title_fullStr 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title_full_unstemmed 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title_short 1899. The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
title_sort 1899. the cellular kinase inhibitor osu-03012 inhibits enterovirus 71 in vitro
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254896/
http://dx.doi.org/10.1093/ofid/ofy210.1555
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