Institute of Organic Chemistry and Biochemistry of the CAS,Czech Republic
Title: Structure-based approaches to novel antiviral compounds
Dr. Nencka is now group leader at the IOCB Prague. He is also a lecturer of Chemical Biology and Basic Principles of Drug Discovery at Palacký University, Olomouc. He got his Mgr. (equivalent of MSc.) in pharmacy from Faculty of Pharmacy in Hradec Králové, Charles University - his master thesis was done at University of Crete, Heraklion, Greece (Prof. Manolis Stratakis). He obtained Ph.D. in organic chemistry from Faculty of Science, Charles University, Prague (Dr. Hubert HÅ™ebabecký, Prof. Antonín Holý group at IOCB Prague) and spent his postdoctoral stay in Laboratory of Medicinal Chemistry, University of Ghent, Belgium (Prof. Serge Van Calenbergh). Among his main research interests are synthesis of novel compounds for treatment of viral diseases and rational design of inhibitors targeted on crucial enzymes
Flaviviruses and picornaviruses are important groups of RNA viruses and both of them contain dangerous human pathogens, which threaten the lives of millions of people around the globe. Among others, Zika virus (ZIKV) has recently emerged as an important danger for human reproduction, causing significant malformations in newborns. Also, Dengue virus (DENV), another member of flaviviruses, causes around 96 millions symptomatic infections every year. On the other hand, human rhinoviruses (HRVs), members of picornaviruses, are probably the most common viruses causing infections in humans, since it is the major cause of common cold.
Our research team is predominantly focused on the structure-based discovery of novel antiviral agents with special attention to these two groups of viruses. Recently, we have performed a study on novel potential antiviral compounds against ZIKV. We prepared a structural model of ZIKV RNA-dependent RNA polymerase in complex with the template and nascent RNAs, Mg2+ ions and accessing nucleoside triphosphate, which should serve as a functional tool for the design of novel nucleoside derivatives as a potential inhibitor of this central enzyme of viral replication. In addition, we have extensively studied potential novel antiviral agents against HRV based on inhibition of phosphatidylinositol 4-kinase IIIb (PI4KB), which is essential host factor required for assembly of replication organelles and the whole viral machinery inside human cells. The lecture will focus on utilization of structural information obtained by X-ray crystallography in the rational design of novel inhibitors of viral replication and try to explain potential strategies to effectively achieve this goal.