NOV 06, 2019 10:30 AM PST

Drug discovery and pharmacology of antivirals targeting drug-resistant influenza viruses

Presented at: Influenza 2019
C.E. Credits: P.A.C.E. CE Florida CE
Speakers
  • Assistant Professor, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona
    Biography
      Dr. Wang received his bachelor degree in chemistry from Wuhan University, China, in 2003. After a one year industry experience in a biotechnology company, he joined Dr. Shaoqin Yao's group at the National University of Singapore in 2004 as a graduate student. His thesis project involves designing and developing chemical probes and inhibitors for matrix metalloproteases. After receiving his master degree in 2006, he moved to the United States and started his PhD study in Dr. William F. DeGrado's laboratory at the University of Pennsylvania. His PhD thesis focuses on rational design of inhibitors targeting drug-resistant influenza A virus M2 proton channels. He is also a major contributor in developing chemical probes to solve the scientific controversy of the drug binding site(s) of M2. After receiving his PhD in chemistry in 2010, he continued as a postdoctoral researcher in the DeGrado lab, first at the University of Pennsylvania and later at the University of California, San Francisco. He started his independent career as an assistant professor at the College of Pharmacy, University of Arizona in 2014. His laboratory mainly focuses on medicinal chemistry and pharmacology of antivirals. Research in the Wang Laboratory is directed towards developing antivirals targeting drug-resistant viruses and emerging viruses, including influenza A and B viruses, enterovirus D68 (EV-D68), EV-A71, coxsackievirus, and polio virus. They are developing inhibitors against multiple viral proteins and use them as chemical probes for target validation. For influenza virus, they have developed inhibitors targeting the M2 proton channel, the viral polymerase PA-PB1 protein-protein interactions, and the hemagglutinin fusion protein. For enteroviruses, they have designed inhibitors targeting the viral capsid VP1 protein, the viral 2A protease, the viral 2C protein, and the viral polymerase. In addition, they are also interested in developing host-targeting antivirals as a means to address drug resistance.

    Abstract:

    The efficacy of current influenza antiviral drugs is compromised by emerging drug resistance. To address this unmet medical need, we have made progress in developing novel influenza antivirals by targeting the drug-resistant mutants of M2 and the viral polymerase. In this presentation, I will introduce our work in designing inhibitors targeting the viral M2-S31N mutant proton channel and the viral polymerase PA-PB1 interactions. The designed M2-S31N inhibitors and the PA-PB1 inhibitors have been shown to inhibit drug resistant influenza viruses with potent antiviral efficacy and a high selectivity index. 


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