Kyeong-Ok Chang
Professor, 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
Research
I have over 25 years of research experience in virology, specifically in viral pathogenesis and the development of preventive and/or therapeutic measures for important human and animal pathogens. Currently, my research focuses on norovirus proteases as potential therapeutic targets with a multi-disciplinary approach, including compound synthesis, functional, structural and inhibitor studies of proteases with medicinal chemists, virologists, and structural biologists. We have published numerous papers describing the design, synthesis, and evaluation of various transition-state inhibitors of viral proteases. Our group demonstrated that some inhibitors showed broad-spectrum antiviral activities against multiple viruses in picornavirus-like supercluster which includes picornaviruses, caliciviruses (norovirus) and coronaviruses. Through these drug development endeavors, recently we have identified anti-norovirus and/or coronavirus protease inhibitors effective in animal models. One of the inhibitors was advanced to the late stage of drug development against a fatal feline coronavirus (feline infectious peritonitis virus, FIPV). The compound was shown to be highly effective in naturally or experimentally infected cats with FIPV. Our group continues to identify new antiviral compounds as well as advancing the current series beyond the preclinical stages.
PubMed search for Dr. Chang
- Galasiti Kankanamalage, A., Kim, Y., Rathnayake, A., Damalanka, V., Weerawarna, P., Doyle, S., Alsoudi, A., Dissanayake, D.M. P., Lushington, G., Mehzabeen, N., Battaile, K., Lovell, S., Chang, K.O., Groutas, W. (2017) Structure-Based Exploration and Exploitation of the S4 Subsite of Norovirus 3CL Protease in the Design of Potent and Permeable Inhibitors. Eur J Med Chem, 126, 502-516.
- Damalanka, V., Kim, Y., Galasiti Kankanamalage, A., Lushington, G., Mehzabeen, N., Battaile, K., Lovell, S., Chang, K.O., and Groutas, W. (2017). Design, Synthesis, and Evaluation of a Novel Series of Macrocyclic Inhibitors of Norovirus 3CL Protease. Eur J Med Chem, 127, 41-61.
- Galasiti Kankanamalage A., Kim, Y., Rathnayake, A., Alliston, K., Butler, M., Cardinale, S., Bowlin, T., Groutas, W., and Chang, K.O. (2017). Design, Synthesis, and Evaluation of Novel Prodrugs of Transition State Inhibitors of Norovirus 3CL Protease. J Med Chem, 60(14):6239-6248.
- Damalanka, V.C., Y. Kim, Galasiti Kankanamalage A.C., Rathnayake, A.D., Mehzabeen, N., Battaile, K.P., Lovell, S., Nguyen, H.N., Lushington, G.H., Chang, K.O., and Groutas. W.C. (2017). Structure-guided Design, Synthesis and Evaluation of Oxazolidinone-based Inhibitors of Norovirus 3CL Protease. Eur J Med Chem. https://doi.org/10.1016/j.ejmech.2017.12.014
- Kim, Y., Oh, C., Shivanna, V., Hesse, R., and Chang, K.O. (2017). Trypsin-Independent Porcine Epidemic Diarrhea Virus US Strain with Altered Virus Entry Mechanism. BMC Veterinary Research, https://doi.org/10.1186/s12917-017-1283-1.
- Pedersen, N.C., Kim, Y., Liu, H., Galasiti Kankanamalage, A.C., Eckstrand, C., Groutas, W.C., Bannasch, M., Meadows, J.M and Chang, K.O. (2017). Efficacy of a 3c-like Protease Inhibitor in Treating Various Forms of Acquired Feline Infectious Peritonitis. Journal of Feline Medicine and Surgery. https://doi.org/10.1177/1098612X17729626.
- Dang, W., Yin, Y., Wang, Y., Wang, W., Su, J., Sprengers, D., van der Laan, L., Felczak, K., Pankiewicz, K., Chang, K.O., Koopmans, M., Metselaar, H., Peppelenbosch, M., and Pan, Q. (2017). Inhibition of calcineurin or IMPDH exerts moderate to potent antiviral activity against norovirus replication. Antimicrobial Agents and Chemotherapy. 61 (11): e01095-17.
- Weerawarna, P.M., Kim, Y., Galasiti Kankanamalage, A.C., Damalanka, V.C., Lushington, G.H., Alliston, K.R., Mehzabeen, N., Battaile, K.P., Lovell, S., Chang, K.O., and Groutas, W.C. (2016). Structure-Based Design and Synthesis of triazole-based macrocyclic inhibitors of norovirus 3CL protease: Structural, biochemical, spectroscopic, and antiviral studies. Eur J Med Chem. 119, 300-318.
- Kim, Y., Liu, H., Hua, D.H., Groutas, W.C., Chang, K.O., Pedersen, N.C. (2016). Protease inhibitor reverses the progression of fatal coronavirus infection in cats. PLoS Pathog. 30;12(3):e1005531.
- Kim, Y, Galasiti Kankanamalage, AC, Damalanka, VC, Weerawarna, PM, Groutas, WC, Chang, KO. (2016). Potent inhibition of enterovirus D68 and human rhinoviruses by dipeptidyl aldehydes and α-ketoamides. Antiviral Res. (2016). 125:84-91
- Galasiti Kankanamalage, A.C., Weerawarna, P.M., Kim, Y., Chang, K.O., Groutas, W.C. (2016). Anti-Norovirus Therapeutics: A Patent Review (2007-2015). Expert Opin Ther Pat. 26(3):297-308.
- Damalanka, V., Kim, Y., Alliston, K., Weerawarna, P., Galasiti Kankanamalage, AC., Lushington, G., Mehzabeen, N., Battaile, K., Lovell, S., Chang, K.O., Groutas, W.C. (2016) Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease. J Med Chem. 59(5):1899-913.
- Weerawarna, PM., Kim, Y., Galasiti Kankanamalage, AC., Damalanka, VC., Lushington, GH., Alliston, KR., Mehzabeen, N., Battaile, KP., Lovell, S., Chang, K.O., Groutas, W.C. (2016). Structure-Based Design and Synthesis of Macrocyclic Inhibitors of Norovirus 3CL Protease: Structural, Biochemical, Spectroscopic, and Antiviral Studies. European Journal of Medicinal Chemistry. 119:300-18.
- Lu, Z, Yokoyama, M., Chen, N., Oka, T., Jung, K., Chang, K.O., Annamalai, T., Wang, Q., Saif, L.J. (2015). Mechanism of cell culture adaptation of an enteric calicivirus, porcine sapovirus Cowden strain. J Virol. 90(3):1345-58.
- Kim Y, Galasiti Kankanamalage A.C., Chang K.O., Groutas, W.C. (2015). Recent Advances in the Discovery of Norovirus Therapeutics. J Med Chem. 8(24):9438-50.
- Shivanna V, Kim Y, Chang KO. (2015). Bile acid-mediated Activation of the Acid Sphingomyelinase Facilitates Endosomal Escape of Porcine Enteric Calicivirus. Virology. 483:218-28.
- Zhang L, Zhang S, Maezawa I, Trushin S, Minhas P, Pinto M, Jin L, Thi KP, Nguyen DT, Yamazaki Y, Kanekiyo T., Bu G, Gateno B, Chang KO, Nath KA, Nemutlu E, Dzeja P, Pang Y, Hua DH, Trushina E. (2015). Modulation of mitochondrial energetics with tricyclic pyrone CP2 averts cognitive decline in multiple transgenic mouse models of familial Alzheimer’s disease. EBioMedicine. 2(4):294-305.
- Kim Y, Shivanna V, Hua DH, Groutas WC, and Chang KO. (2015). Broad-spectrum protease inhibitors against 3C-like proteases of feline coronaviruses and feline caliciviruses. J Virol. 89(9):4942-50
- Galasiti Kankanamalage AC., Uy WP, Mandadapu SR, Alliston KR, Chang KO, Kim Y, Lovell S, Groutas WC. (2015). Structure-Based Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic and Cell-Based Studies. J Med Chem. 58(7):3144-55