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Conference Paper: The Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro

TitleThe Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro
Authors
Issue Date2018
PublisherOxford University Press (OUP). The Journal's web site is located at http://ofid.oxfordjournals.org/
Citation
IDWeek 2018, the combined annual meeting of IDSA (Infectious Diseases Society of America), SHEA, HIVMA, and PIDS: Advancing Science, Improving Care, San Francisco, CA, USA, 3-7 October 2018. IDWeek 2018 Abstracts in Open Forum Infectious Diseases, 2018, v. 5 n. Suppl. 1, p. S545 How to Cite?
AbstractBackground: Enterovirus 71 (EV-71) is a non-enveloped, 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 (IC50) 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 2µM 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 2µM 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.
DescriptionPoster Abstract Session 224: Antiviral Therapies - no. 1899
Persistent Identifierhttp://hdl.handle.net/10722/274161
ISSN
2017 Impact Factor: 3.24

 

DC FieldValueLanguage
dc.contributor.authorChan, JFW-
dc.contributor.authorTsang, OL-
dc.contributor.authorZou, Z-
dc.contributor.authorChik, KKH-
dc.contributor.authorYuan, S-
dc.contributor.authorChu, H-
dc.contributor.authorLau, SKP-
dc.contributor.authorYuen, KY-
dc.date.accessioned2019-08-18T14:56:17Z-
dc.date.available2019-08-18T14:56:17Z-
dc.date.issued2018-
dc.identifier.citationIDWeek 2018, the combined annual meeting of IDSA (Infectious Diseases Society of America), SHEA, HIVMA, and PIDS: Advancing Science, Improving Care, San Francisco, CA, USA, 3-7 October 2018. IDWeek 2018 Abstracts in Open Forum Infectious Diseases, 2018, v. 5 n. Suppl. 1, p. S545-
dc.identifier.issn2328-8957-
dc.identifier.urihttp://hdl.handle.net/10722/274161-
dc.descriptionPoster Abstract Session 224: Antiviral Therapies - no. 1899-
dc.description.abstractBackground: Enterovirus 71 (EV-71) is a non-enveloped, 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 (IC50) 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 2µM 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 2µM 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.-
dc.languageeng-
dc.publisherOxford University Press (OUP). The Journal's web site is located at http://ofid.oxfordjournals.org/-
dc.relation.ispartofOpen Forum Infectious Diseases-
dc.relation.ispartofIDWeek 2018-
dc.titleThe Cellular Kinase Inhibitor OSU-03012 Inhibits Enterovirus 71 In Vitro-
dc.typeConference_Paper-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailLau, SKP: skplau@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityLau, SKP=rp00486-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.doi10.1093/ofid/ofy210.1555-
dc.identifier.hkuros301241-
dc.identifier.volume5-
dc.identifier.issueSuppl. 1-
dc.identifier.spageS545-
dc.identifier.epageS545-
dc.publisher.placeUnited Kingdom-

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