Jun Wang, PhD

Associate Professor, Pharmacology and Toxicology

Jun Wang, PhD, is an associate professor of Pharmacology and Toxicology at the UA College of Pharmacy. The research conducted in the Wang Laboratory is focused on developing antivirals targeting drug-resistant viruses and emerging viruses, including influenza A and B viruses, enterovirus D68 (EV-D68), EV-A71, coxsackievirus, poliovirus, and the recently emerged SARS-CoV-2. We are developing inhibitors against multiple viral proteins and using them as chemical probes for target validation, both in vitro and in vivo. 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. For SARS-CoV-2, we recently identified a few interesting main protease inhibitors. 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 are 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. We currently have multiple positions opening at all levels (postdoc, graduate student, technician, and undergraduate). Candidates with background or interest in medicinal chemistry, pharmacology, assay development, high-throughput screening, molecular biology, and virology are all welcomed! Only know a little about viruses? Don't worry, we will teach you everything you need to know and we will grow together! 

Current Research in the Wang Laboratory Covers the Following Areas:

  1. Drug discovery and pharmacology of SARS-CoV-2. To combat the COVID-19 pandemic, we recently initiated several projects in developing antivirals for SARS-CoV-2. We are pursuing several drug targets including the main protease (Mpro or 3CLpro), the papain-like protease (PLpro), the nucleoprotein, and the polymerase. The goal is to identify broad-spectrum antiviral drug candidates with a high genetic barrier to drug resistance. For this, we rely on high-throughput screening and structure-based drug design to inform the lead optimization through iterative cycles of design, synthesis, and pharmacological characterization. We are also interested in profiling the genetic barrier to drug resistance of our leads and apply the knowledge to guide the design of resistance avoiding antivirals. We recently made progress in discovering several promising Mpro inhibitors including boceprevir, GC-376, calpain inhibitors II and XII. Boceprevir, calpain inhibiotrs II and XII represent novel Mpro inhibitors that are distinct from previously reported Mpro inhibitors. All four compounds showed potent enzymatic inhibition and cellular antiviral activity against Mpro and infectious SARS-CoV-2, respectively. In collaboration with Dr. Yu Chen at the University of South Florida we solved multiple X-ray crystal structures of Mpro with the hits we identified. These high-resolution X-ray crystal structures provides a foundation for the designing of next-generation of Mpro inhibitors.
  2. 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.
  3. 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 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.
  4. Antiviral drug discovery targeting emerging and re-emerging viruses such as enterovirus, coxsackievirus, and poliovirus. 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 poliovirus. We recently made progress in targeting the VP1 capsid protein, 2A protease, 2C protein and the viral polymerase of EV-D68.
  5. 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 to study the mechanism of resistance and the consequence of drug resistance. The understanding of drug resistance will help inform the design of antiviral drugs with a higher genetic barrier to drug resistance.

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.

View UA Profile

Education & Post Graduate Training: 

BS, Chemistry, Wuhan University (China), 2003
MS, Chemistry, National University of Singapore, 2006
PhD, Chemistry, University of Pennsylvania, 2010
Postdoc, Pharmacutical Chemistry, University of California, San Francisco, 2014

 

Select Publications

2020

Hu, Y., R. Musharrafieh, M. Zheng, and J. Wang, "Enterovirus D68 Antivirals: Past, Present, and Future.", ACS Infect Dis, vol. 6, issue 7, pp. 1572-1586, 2020 07 10. PMID: 32352280
Ma, C., M. Dominic Sacco, B. Hurst, J. Alma Townsend, Y. Hu, T. Szeto, X. Zhang, B. Tarbet, M. Thomas Marty, Y. Chen, et al., "Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease.", Cell Res, vol. 30, issue 8, pp. 678-692, 2020 08. PMCID: PMC7294525  PMID: 32541865
Musharrafieh, R., P. Lagarias, C. Ma, R. Hau, A. Romano, G. Lambrinidis, A. Kolocouris, and J. Wang, "Investigation of the Drug Resistance Mechanism of M2-S31N Channel Blockers through Biomolecular Simulations and Viral Passage Experiments.", ACS Pharmacol Transl Sci, vol. 3, issue 4, pp. 666-675, 2020 Aug 14. PMCID: PMC7432665  PMID: 32832869
Zhang, J., Y. Hu, N. Wu, and J. Wang, "Discovery of Influenza Polymerase PA-PB1 Interaction Inhibitors Using an Split-Luciferase Complementation-Based Assay.", ACS Chem Biol, vol. 15, issue 1, pp. 74-82, 2020 01 17. PMCID: PMC7028398  PMID: 31714745

2019

Musharrafieh, R., C. Ma, J. Zhang, Y. Hu, J. M. Diesing, M. T. Marty, and J. Wang, "Validating Enterovirus D68-2A as an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2A Inhibitor.", J Virol, vol. 93, issue 7, 2019 04 01. PMCID: PMC6430540  PMID: 30674624
Ma, C., Y. Hu, J. Zhang, R. Musharrafieh, and J. Wang, "A Novel Capsid Binding Inhibitor Displays Potent Antiviral Activity against Enterovirus D68.", ACS Infect Dis, vol. 5, issue 11, pp. 1952-1962, 2019 11 08. PMCID: PMC7167248  PMID: 31532189
Thomaston, J. L., Y. Wu, N. Polizzi, L. Liu, J. Wang, and W. F. DeGrado, "X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case.", J Am Chem Soc, vol. 141, issue 29, pp. 11481-11488, 2019 07 24. PMCID: PMC7405929  PMID: 31184871
Musharrafieh, R., J. Zhang, P. Tuohy, N. Kitamura, S. Sai Bellampalli, Y. Hu, R. Khanna, and J. Wang, "Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68).", J Med Chem, vol. 62, issue 8, pp. 4074-4090, 2019 04 25. PMID: 30912944

2018

Thomaston, J. L., N. F. Polizzi, A. Konstantinidi, J. Wang, A. Kolocouris, and W. F. DeGrado, "Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters.", J Am Chem Soc, vol. 140, issue 45, pp. 15219-15226, 2018 11 14. PMCID: PMC6497056  PMID: 30165017
Zhang, J., Y. Hu, C. Foley, Y. Wang, R. Musharrafieh, S. Xu, Y. Zhang, C. Ma, C. Hulme, and J. Wang, "Exploring Ugi-Azide Four-Component Reaction Products for Broad-Spectrum Influenza Antivirals with a High Genetic Barrier to Drug Resistance.", Sci Rep, vol. 8, issue 1, pp. 4653, 2018 03 15. PMCID: PMC5854701  PMID: 29545578