Jun Wang, PhD

Assistant Professor, Pharmacology and Toxicology

Jun Wang, PhD Assistant Professor, Pharmacology and Toxicology 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. We are developing inhibitors against multiple viral proteins and use them as chemical probes for target validation. For influenza virus, we have developed inhibitors targeting the M2 proton channel, the viral polymerase PA-PB1 protein-protein interactions, and the hemagglutinin fusion protein. For enteroviruses, we have designed inhibitors targeting the viral capsid VP1 protein, the viral 2A protease, the viral 2C protein, and the viral polymerase. In addition, we are also interested in developing host-targeting antivirals as a means to address drug resistance.

Techniques implemented in the Wang laboratory include but not limited to structure-based drug design, high-throughput screening, medicinal chemistry, electrophysiology, peptide chemistry, biophysics and virology. We are a diverse group and researchers in the Wang Lab have opportunity to explore all aspects of pre-clinical drug discovery in the same lab starting from molecular-level design to in vivo animal model studies.

Students Seeking Research Opportunities

Please contact Dr. Wang (junwang@pharmacy.arizona.edu) if you are interested in exploring research opportunities in the Wang Laboratory. Undergraduates and PharmD students are particularly encouraged to apply. Don't know much about chemistry or virology? Don't worry we will teach you everything you need to know, at the same time, we expect to learn things from you as well!

Current Research in the Wang Laboratory Covers the Following Areas:

  1. Discovery of broad-spectrum antivirals targeting influenza viruses, especially multi-drug resistant influenza viruses. Currently, the Wang lab is exploring both viral proteins and host factors as antiviral drug targets. As an example, the rationally designed first-in-class AM2-S31N inhibitors have shown potent antiviral activity against multiple human influenza A strains, including the ones that are resistant to oseltamivir. In another example, the Wang lab has identified several host-targeting antivirals from a high-throughput screening campaign, and they have shown broad-spectrum antiviral activity against both influenza A and B strains with mechanisms distinct from that of known antiviral drugs. These novel hits will not only lead to the discovery of new antiviral drug targets but also serve as tool compounds to help understand the mechanism of drug resistance.
  2. Drug discovery targeting the influenza virus polymerase complex. The influenza virus polymerase complex is highly conserved and it is a high profile antiviral drug target. From in silico screening, the Wang lab has identified several interesting lead compounds that target the polymerase complex. The hit compounds have shown broad-spectrum antiviral activity against both influenza A and B viruses and have displayed a high genetic barrier to drug resistance. In addition, we recently developed the split-luciferase complementation (SLC) assay for the detection of interaction between influenza polymerase PA-PB1 subunits. Using this assay in a pilot screening, we identified multiple hits with broad-spectrum antiviral activity. We are currently pursuing in vivo mouse model studies with the advanced lead compounds.
  3. Antiviral drug discovery targeting emerging and re-emerging viruses such as enterovirus, coxsakievirus, and polio virus. Taking advantage of the antiviral drug discovery platform they have built through the studies of influenza viruses, the Wang lab is transforming this platform to discover both direct-acting antiviral and host-targeting antiviral for enteroviruses including enterovirus D68 (EV-D68), EV-A71, coxsackievirus, and polio virus. We recently made progress in targeting the VP1 capsid protein, 2A protease, 2C protein and the viral polymerase of EV-D68.
  4. Understanding the mechanism of drug resistance. Many antiviral drugs fail because of drug resistance. Therefore, it is imperative to understand the mechanism of drug resistance and device countermeasures before resistance emerges. In this regard, a significant amount of work is devoted in studying the mechanism of resistance and the consequence of drug resistance. We hope the understanding of drug resistance will help us develop antiviral drugs with a higher genetic barrier to drug resistance. Our primary strengths are medicinal chemistry and pharmacology. We collaborate with computational chemists and structural biologists to help us achieve molecular level understanding of drug action.

The Wang laboratory always welcomes enthusiastic persons at all levels (undergraduate, graduate, postdoc) to join their team. Please email Dr. Wang at junwang@pharmacy.arizona.edu for job opportunities. Undergraduate students and PharmD students are particularly encouraged to apply.

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Education & Post Graduate Training: 

BS, Chemistry, Wuhan University (China), 2003
MS, Chemistry, National University of Singapore, 2006
PhD, Chemistry, University of Pennsylvania, 2010

 

Select Publications

2018

Wang, Y., Y. Hu, S. Xu, Y. Zhang, R. Musharrafieh, R. Kin Hau, C. Ma, and J. Wang, "In Vitro Pharmacokinetic Optimizations of AM2-S31N Channel Blockers Led to the Discovery of Slow-Binding Inhibitors with Potent Antiviral Activity against Drug-Resistant Influenza A Viruses.", J Med Chem, 2018 Jan 17.

2017

Li, F., Y. Hu, Y. Wang, C. Ma, and J. Wang, "Expeditious Lead Optimization of Isoxazole-Containing Influenza A Virus M2-S31N Inhibitors Using the Suzuki-Miyaura Cross-Coupling Reaction.", J Med Chem, vol. 60, issue 4, pp. 1580-1590, 2017 Feb 23. PMID: 28182419
Hu, Y., J. Zhang, R. Ghassan Musharrafieh, C. Ma, R. Hau, and J. Wang, "Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.", Antiviral Res, vol. 145, pp. 103-113, 2017 Sep. PMCID: PMC5599177  PMID: 28778830

2016

Ma, C., F. Li, R. Ghassan Musharrafieh, and J. Wang, "Discovery of cyclosporine A and its analogs as broad-spectrum anti-influenza drugs with a high in vitro genetic barrier of drug resistance.", Antiviral Res, vol. 133, pp. 62-72, 2016 Sep. PMCID: PMC5026937  PMID: 27478032
Li, F., C. Ma, W. F. DeGrado, and J. Wang, "Discovery of Highly Potent Inhibitors Targeting the Predominant Drug-Resistant S31N Mutant of the Influenza A Virus M2 Proton Channel.", J Med Chem, vol. 59, issue 3, pp. 1207-16, 2016 Feb 11. PMCID: PMC4829348  PMID: 26771709