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Introduction of group leader
Office phone: +82-31-8018-8180
Office location: R4.25-2
My laboratory is interested in applied molecular virology of hepatitis B and C viruses (HBV & HCV). Research tools and assays were developed supporting HTS campaigns and mechanism of action (MoA) studies. With the infectious HCV cell culture system, more than 250,000 compounds were screened, viral RNA replication inhibitors excluded and HCV E1/E2 entry inhibitor included. Thereby, antivirals have been identified acting on viral entry and secretion. Surprisingly, one compound series exclusively inhibits HCV genotype 2; mapping of the genotype determining region and MoA studies are ongoing. Another compound series, which inhibits major HCV genotypes, is currently being characterized and a lead optimization program is being pursued, which is financially supported by the Korea Drug Development Fund (KDDF). To date, state-of-the-art HCV therapies cost more than USD 100,000; this high economic burden will limit access to therapies. Consequently, we are looking into affordable alternatives, e.g. screening and characterization of natural compounds, and we seek non-profit organizations to jointly develop drugs for patient in needs.
We are also on a quest to identify and characterize drugs with a novel MoA, which potentially could cure chronic hepatitis B. In collaboration with a local lab and an international pharmaceutical company, we screened for pre-genomic RNA encapsidation inhibitors and for immunomodulator restoring innate immunity in chronically HBV infected hepatocytes. Furthermore, in collaboration with a German lab, we developed a robust infectious HBV cell culture system in 384-well plates suitable for HTS. With this cutting-edge technology, small molecule compound libraries will be screened to identify and characterize inhibitors targeting HBV entry, capsid disassembly/trafficking, cccDNA synthesis, etc.
With the re-emergence of the Ebola virus in Africa and the quick spread to other countries, this pathogen has been recognized as a global threat. In order to tackle Ebola, we devised strategies to identify immunomodulator, replication and entry inhibitors. Currently, we are looking for external collaboration partners to develop HTS assays and to characterize identified hit compounds.
Characterization and structure-activity relationship study of iminodipyridinopyrimidines as novel hepatitis C virus inhibitor.
Park DS, Jo E, Choi J, Lee M, Kim S, Kim HY, Nam J, Ahn S, Hwang JY, Windisch MP
Eur J Med Chem. 2017 Nov 10;140:65-73
A Novel Inhibitor IDPP Interferes with Entry and Egress of HCV by Targeting Glycoprotein E1 in a Genotype-Specific Manner.
Lee M, Yang J, Jo E, Lee JY, Kim HY, Bartenschlager R, Shin EC, Bae YS, Windisch MP
Sci Rep. 2017 Mar 23;7:44676
In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.
ElHefnawi M, Kim T, Kamar MA, Min S, Hassan NM, El-Ahwany E, Kim H, Zada S, Amer M, Windisch MP
PLoS One. 2016 Jul 21;11(7):e0159211
Micrococcin P1, a naturally occurring macrocyclic peptide inhibiting hepatitis C virus entry in a pan-genotypic manner.
Lee M, Yang J, Park S, Jo E, Kim HY, Bae YS, Windisch MP
Antiviral Res. 2016 Aug;132:287-95
Benzothiazepinecarboxamides: Novel hepatitis C virus inhibitors that interfere with viral entry and the generation of infectious virions.
Kim HY, Kong S, Oh S, Yang J, Jo E, Ko Y, Kim SH, Hwang JY, Song R, Windisch MP
Antiviral Res. 2016 May;129:39-46