1899. The cellular kinase inhibitor OSU-03012 inhibits enterovirus 71 in vitro
Session: Poster Abstract Session: Antiviral Therapies
Saturday, October 6, 2018
Room: S Poster Hall
Background: 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.

Jasper Chan, MD1,2, Jessica Tsang, BSc2, Zijiao Zou, MPhil2, Kenn Chik, MMedSc2, Shuofeng Yuan, PhD2, Hin Chu, PhD2, Susanna Lau, MD1,2 and Kwok-Yung Yuen, MD1,2, (1)State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, Hong Kong, (2)Department of Microbiology, The University of Hong Kong, Hong Kong, Hong Kong

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 .

J. Tsang, None

Z. Zou, None

K. Chik, None

S. Yuan, None

H. Chu, None

S. Lau, None

K. Y. Yuen, None

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