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College of Veterinary Medicine

Kyeong-Ok Chang

 Associate Professor, Veterinary Virology

DVM (1989), Seoul National University
MS (1991), Seoul National University
PhD (1999), The Ohio State University

Phone: 785-532-3849
Fax: 785-532-4039
Email: kchang@vet.ksu.edu

My background includes veterinary medicine and microbiology mainly working on animal and human diseases especially ones due to infectious agents. My research focus has been on the development of therapeutic small molecules against various viruses including noroviruses, influenza virus and rotaviruses with in vitro screening system and animal models such as (gnotobiotic) pigs and mice. For norovirus research, we established cell-based replicon system for uncultivable human noroviruses and demonstration of feasibility of the system with various potential antinorovirals including interferons (with or without a nanogel delivery), ribavirin and other commercially available or newly synthesized compounds. These developments have enabled us to initiate a comprehensive plan aimed at developing anti-noroviral therapeutics in cooperation with medicinal chemists, virologists, structural biologists and commercial partners. Currently our research focuses on viral proteases as potential therapeutic targets with functional, structural and inhibitor studies of proteases. We have recently described the design, synthesis, and evaluation of transition state inhibitors of norovirus proteases. Some of the inhibitors are highly potent (EC50, < 0.01 µM) and selective (CC50, > 100 µM), have been characterized for spectrum of antiviral activity against noroviruses and related caliciviruses, mechanism of action with structural resolution of binding, viral resistance, preliminary absorption, distribution, metabolism and excretion (ADME) properties, tolerability, and oral availability in rats. We are pursuing further development of the identified inhibitors as specific norovirus therapeutics. Those inhibitors were also effectively inhibited viruses in picornavirus-like supercluster which include picornavirus, caliciviruses and coronaviruses in enzyme and cell based assays. Thus, we are pursuing the development of broad-spectrum antivirals against important human and animal viruses in the cluster.

Selected Publications

PubMed search for Dr. Chang

Yunjeong Kim, William C.Groutas, and Kyeong-Ok Chang. 2013. Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease. Antiviral Res. Antiviral Res. Feb;97(2):161-8.

Daisuke Takahashi, Yasuaki Hiromasa, Yunjeong Kim, Asokan Anbanandam, Kyeong-Ok Chang and Om Prakash. 2013. Structural and dynamics characterization of norovirus protease. Protein Science. Protein Sci. Mar;22(3):347-57.

Mandadapu, S. R.; Tiew, K-C.; Gunnam, M. R.; Alliston, K. R.; Kim, Y.; Chang, K.O.; Groutas, W. C. 2012. Inhibition of Noroviruses by Aldehyde-Derived Bisulfite Salts. Bioorg Med Chem Lett. 23: 62-65

Yunjeong Kim, Scott Lovell, Kok-Chuan Tiew, Sivakoteswara R. Mandadapu, Kevin R. Alliston, Kevin P. Battaile, William C.Groutas, and Kyeong-Ok Chang. 2012. Novel Broad-Spectrum Antivirals against 3C or 3C-like proteases of Picornaviruses, Noroviruses and Coronaviruses. Journal of Virology. 86(21):11754-62.

Jung, K., Wang, Q.H., Kim, Y., Scheuer, K., Zhang, Z., Chang, K.O., Saif, L.J. 2012. The effects of simvastatin or interferon-α on infectivity of human norovirus in the gnotobiotic pig model for the study of antivirals. PLoS ONE. 7(7):e41619

Jeffrey W. Perry, Mohammad Ahmed, Kyeong-Ok Chang, Nicholas J. Donato, Hollis D. Showalter, and Christiane E. Wobus. 2012. A Small Molecule Deubiquitinase Inhibitor has Anti-Viral Effects through Induction of the Unfolded Protein Response. PLoS Pathog. 8(7):e1002783

Sivakoteswara Rao Mandadapu, Pathum M. Weerawarna, Mallikarjuna Reddy Gunnam, Kevin R. Alliston, Gerald H. Lushington, Yunjeong Kim, Kyeong-Ok Chang, William C. Groutas. 2012. Potent Inhibition of Norwalk Virus 3C Protease by Peptidyl α-Ketoamides and α-Ketoheterocycles Bioorg Med Chem Lett. 22(14):4820-6

Laxman Pokheil, Yunjeong Kim, Thi D. T. Nguyen, Allan M. Prior, Jianyu Lu, Kyeong-Ok Chang, and Duy H. Hua. Synthesis and Antinorovirus Activity of Pyranobenzopyrone Compounds. 2012. Bioorg Med Chem Lett. 22(10):3480-4.

Yunjeong Kim, David George, Allan M. Prior, Keshar Prasain, Shuanghong Hao, Duy D. Le, Duy H. Hua and Kyeong-Ok Chang. 2012. Novel triacsin C analogs as potential antivirals against rotavirus infections. Eur J Med Chem. 50:311-8.

Kyeong-Ok Chang, Daisuke Takahashi, Om Prakash, and Yunjeong Kim. 2012. Characterization of Proteases from Norovirus Genogroup I and II with the Fluorescence Resonance Energy Transfer Assay. Virology. 20;423(2):125-33

Yunjeong Kim, and Kyeong-Ok Chang. 2011. Inhibition of Rotavirus replication by Bile Acids through Farnesoid X Recepter. J Virol. 85(23):12570-7.

Kok-Chuan Tiew, Guijia He, Sridhar Aravapalli, Sivakoteswara Rao Mandadapu, Mallikarjuna Reddy Gunnam, Kevin R. Alliston, Gerald H. Lushington, Yunjeong Kim, Kyeong-Ok Chang, William C. Groutas. 2011. Design, Synthesis, and Evaluation of Inhibitors of Norwalk Virus 3C Protease. Bioorg Med Chem Lett. 21(18):5315-9.

Yunjeong Kim, Mahendra Thapa, Duy H Hua and K.O. Chang. 2011. Biodegradable nanogels as oral delivery systems for low dose interferons in norovirus infection. Antiviral Res. 89(2):165-73.

Chang, K.O. The role of cholesterol pathway in norovirus replication. 2009. J Virol. Oct 25; 83(17):8587-95.

Patton, J.B., R. Rowland, D. Yoo, and K.O. Chang. 2009. Modulation of CD163 receptor expression and replication of porcine reproductive and respiratory syndrome virus in porcine macrophage. Virus Res. Mar;140(1-2):161-71.

Chang, K.O., D.W. George, J.B. Patton, K.Y. Green, S.V. Sosnovtsev. 2008. Leader of the capsid protein in feline calicivirus promotes the replication of Norwalk virus in cell culture. J Virol. 82(19):9306-17.

Chang, K.O., George, D.W. 2007. Interferons and Ribavirin Effectively Inhibit Norwalk Virus Replication in the Replicon-Bearing cells. J Virol. 82(19):9306-17.

Chang, K.O., George, D.W. 2007. Bile acids promote the replication of hepatitis C virus in the replicon harboring cells. J Virol. 81(18):9633-40.

Chang, K.O., S.V. Sosnovtsev, G. Belliot, K.Y. Green. 2006. Stable expression of a Norwalk virus RNA replicon in a human hepatoma cell line. Virology. 353(2):463-73.

Chang, K.O., S.V. Sosnovtsev, G. Belliot, Q. Wang, L.J. Saif, K.Y. Green. 2005. A reverse genetics system for porcine enteric calicivirus is dependent on bile acids for recovery of virus in cultured cells. J Virol. 79(3):1409-16.

Wobus, C.E., S.M. Karst, A. Krug, K.O. Chang, S.V. Sosnovtsev, G. Belliot, J.M. Mackenzie, K.Y. Green, H.W. Virgin. 2004. Replication of a Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biology . 2(12):e432.

Chang, K.O., S.V. Sosnovtsev, G. Belliot, Y. Kim, L.J. Saif, K.Y. Green. 2004. Bile acids are essential for porcine enteric calicivirus replication in association with down-regulation of Stat1. Proc Natl Acad Sci U S A, 101(23):8733-8.