Donghoon Chung, Ph.D.
Donghoon Chung, Ph.D.
., Korea University
Address: CTRB, Room 617
Our lab discovers small molecules that can probe the biology of viruses. Our primary interests focus on positive strand RNA viruses as they include many medically important pathogens such as alphaviruses, dengue viruses, West Nile virus, HCV and SARS-CoV. Understanding of the biology of the viruses would provide us insight into the control of the diseases.
To investigate the alphavirus replication mechanism, we used a high-throughput screen campaign, and discovered a few novel compounds that inhibit alphavirus replication. Mechanism of action studies for the compounds revealed that each compound affects a specific step during the virus replication cycle. Currently we are focusing on two compounds: 1) a replicase inhibitor specifically targeting two viral replicase components, and 2) an entry inhibitor targeting a cellular protein that is exploited by the virus.
Regarding the replicase inhibitor, we found that the compound inhibits viral RNA synthesis by targeting the non-structural proteins 2 and 4, key components of the viral RNA replicase complex. Interestingly, the biological functions of the compound-targeting domains remain unknown. Hence, we are investigating the function of the domains during the viral replication by using the compound.
With the entry inhibitor, we found that the activity is cell line-dependent, indicating that alphaviruses use different entry mechanisms in different cell types (neuronal cells vs. fibroblast cells). We are studying the precise entry mechanisms for alphavirus depending on the host cell types.
We are also interested in pursuing the development of these molecules into therapeutics for alphaviral diseases.
1. Chung, D.H., C.B. Jonsson, N.A. Tower, Y.K. Chu, E. Sahin, J.E. Golden, J.W. Noah, C.E. Schroeder, J.B. Sotsky, M.I. Sosa, D.E. Cramer, S.N. McKellip, L. Rasmussen, E.L. White, C.S. Schmaljohn, J.G. Julander, J.M. Smith, C.M. Filone, J.H. Connor, Y. Sakurai, and R.A. Davey, Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2. PLoS pathogens, 2014(6): p. e1004213. PMCID: 24967809
2. Chung, D.H., A. Vastermark, J.V. Camp, R. McAllister, S.K. Remold, Y.K. Chu, C. Bruder, and C.B. Jonsson, The murine model for Hantaan virus-induced lethal disease shows two distinct paths in viral evolutionary trajectory with and without ribavirin treatment. Journal of virology, 2013(20): p. 10997-1007. PMCID: 23903835
3. Chung, D.H., B.P. Moore, D.S. Matharu, J.E. Golden, C. Maddox, L. Rasmussen, M.I. Sosa, S. Ananthan, E.L. White, F. Jia, C.B. Jonsson, and W.E. Severson, A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus. Virol J, 2013. 10: p. 19. PMCID: PMC3621174
4. Moore, B.P., D.H. Chung, D.S. Matharu, J.E. Golden, C. Maddox, L. Rasmussen, J.W. Noah, M.I. Sosa, S. Ananthan, N.A. Tower, E.L. White, F. Jia, T.E. Prisinzano, J. Aube, C.B. Jonsson, and W.E. Severson, (S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a small molecule inhibitor probe for the study of respiratory syncytial virus infection. Journal of Medicinal Chemistry, 2012(20): p. 8582-7. PMCID: PMC3506029
5. Chung, D.H., C.B. Jonsson, C. Maddox, S.N. McKellip, B.P. Moore, M. Heil, E.L. White, S. Ananthan, Q. Li, S. Feng, and L. Rasmussen, HTS-driven discovery of new chemotypes with West Nile Virus inhibitory activity. Molecules (Basel, Switzerland), 2010(3): p. 1690-704. PMCID: 20336008