| Autor: |
Sari IP; Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.; Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan., Ortiz CLD; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Taipei 11529, Taiwan.; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.; Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan., Yang LW; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Taipei 11529, Taiwan.; Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan., Chen MH; Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan., Perng MD; Institute of Molecular Medicine, College of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan., Wu TY; Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan. |
| Abstrakt: |
Nipah virus (NiV) is known to be a highly pathogenic zoonotic virus, which is included in the World Health Organization Research & Development Blueprint list of priority diseases with up to 70% mortality rate. Due to its high pathogenicity and outbreak potency, a therapeutic countermeasure against NiV is urgently needed. As NiV needs to be handled within a Biological Safety Level (BSL) 4 facility, we had developed a safe drug screening platform utilizing a baculovirus expression vector system (BEVS) based on a NiV-induced syncytium formation that could be handled within a BSL-1 facility. To reconstruct the NiV-induced syncytium formation in BEVS, two baculoviruses were generated to express recombinant proteins that are responsible for inducing the syncytium formation, including one baculovirus exhibiting co-expressed NiV fusion protein (NiV-F) and NiV attachment glycoprotein (NiV-G) and another exhibiting human EphrinB2 protein. Interestingly, syncytium formation was observed in infected insect cells when the medium was modified to have a lower pH level and supplemented with cholesterol. Fusion inhibitory properties of several compounds, such as phytochemicals and a polysulfonated naphthylamine compound, were evaluated using this platform. Among these compounds, suramin showed the highest fusion inhibitory activity against NiV-induced syncytium in the baculovirus expression system. Moreover, our in silico results provide a molecular-level glimpse of suramin's interaction with NiV-G's central hole and EphrinB2's G-H loop, which could be the possible reason for its fusion inhibitory activity. |
