Jana Pokorna completed PhD in biochemistry from Charles University in Prague in 2013. She works as an Postdoctoral Fellow at the Institute of Organic Chemistry and Biochemistry ASCR, v.v.i.. Her research interests are activity, inhibition, drug and resistance development focusing on HIV protease and neuraminidase from the Influenza virus. She published 11 peer viewed papers and she is the author of 3 patents.
Influenza is an acute viral infection that can cause serious complications and death, especially among elderly individuals and patients at risk. Neuraminidase, which plays an essential role in virus replication, is the main influenza drug target. At present, two neuraminidase inhibitors (NAIs) are licensed worldwide for therapeutic and prophylactic uses (oseltamivir marketed as Tamiflu and zanamivir, Relenza) and two others have been authorized in various countries for the emergency treatment during pandemics. However, drug resistant viruses readily emerge because of the high mutation rate of their RNA dependent RNA polymerase. Indeed, resistance to oseltamivir, the most prescribed NAI, was detected not only during treatment and prophylaxis, but also in influenza virus variants in untreated individuals. Novel neuraminidase inhibitor resistance substitutions I223V and S247N alone or in combination with a major oseltamivir resistance mutation H275Y have been observed recently in the 2009 pandemic H1N1 viruses. We overexpressed the ectodomain of the wild type neuraminidase from the influenza virus A/California/07/2009 (H1N1) as well as recombinants containing H275Y, I223V, and S247N single mutation and the H275Y, I223V and H275Y, S247N double mutants in Drosophila Schneider S2 cells and purified them by one-step purification using a streptavidin derivative. In order to quantify the level of resistance we enzymologically characterized these enzymes with the set of in-house designed and synthesized derivatives of oseltamivir. Thermodynamic analyses of oseltamivir binding to neuraminidase monomutants were performed by protein microcalorimetry. Finally, we crystallized neuraminidase variants in complexes with oseltamivir to structurally explain the resistance mechanism.
Ya-Yzu Chang is a Public Health Officer of the Department of Division of Preparedness and Emerging Infectious Disease in Taiwan Centers for Disease Control. She is responsible for policy making of influenza prevention and control and has handled experiences on 2009 H1N1 pandemic influenza and H7N9 influenza in Taiwan.
The 2015-2016 influenza season, was a tough period for Taiwan, having 1932 confirmed severe and complicated influenza cases including 328 estimated deaths. Most severe cases (about 77%) were infected with influenza A (H1N1) pdm09 virus. The majority of severe complicated influenza cases and deaths were adult aged 50-64 years. The incidences among all age groups were highest compared to the same period in the last 3 years, especially in the 50-64 age group. The main attacked age group changed from 65 years above to 50-64 years, similar demographic pattern seen in 2009 H1N1 pandemic. The government-funded influenza vaccination program in 2015-2016, following the international consensus, mainly targeted the elders aged more than 65 years, children aged six months through elementary school students and people aged above 50 years with chronic medical conditions. As a result, most people aged 50-64 years have not received influenza vaccines. In addition, the coverage rate of people with chronic diseases was only about 9%. Due to these reasons, in 2016/17 season, we plan to increase the purchase of influenza vaccines and vaccination points, as well as the awareness of the public, to improve the vaccination coverage rates and subsequently lower influenza incidence among people with chronic diseases.