Title: Structure-based Antiviral Drug Discovery: Case Studies of Anti-Influenza, HIV and Hepatitis Agents
Presenter: Dr. CHEN Xiaowu
University: Molecular modeling and structure-based drug discovery, Gilead Sciences, Foster City, California, USA
Time: 09:30-10:30, December 24, 2012
Venue: Room A203, Institute of Microbiology, Chinese Academy of Sciences
Abstract: Viral diseases pose significant threats to humanity. Influenza, HIV, and hepatitis infections account for majority of deadly viral diseases. So far Tamiflu is the only oral anti-influenza drug with broad spectrum activity. During the discovery of Tamiflu at Gilead, an unusual hydrophobic-polar π interaction between charged amino acids of influenza neuraminidase and hydrophobic moiety of Tamiflu has been identified, such interaction is crucial for Tamiflu’s potency. This observation is against conventional thinking in terms of molecular interactions and may provide an additional dimension in future molecular interaction and drug design. Hepatitis C NS3 protease is another interesting viral target that has attracted significant effort from both academia and pharmaceutical industry. A scaffold-dependent structure-activity relationship (SAR) have been predicted by molecular modeling and validated by experimental results. Details of these discoveries will be discussed.