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David Frick

  • Professor, Chemistry & Biochemistry

Education

  • Postdoctoral, Harvard Medical School
  • PhD, Johns Hopkins University
  • BA, Franklin & Marshall College

Teaching Schedule

Course Num Title Meets
CHEM 602-001 Biochemistry: Cellular Processes MW 3:30pm-4:45pm
CHEM 602G-001 Biochemistry: Cellular Processes MW 3:30pm-4:45pm
CHEM 604-001 Biochemistry: Metabolism MWF 1:30pm-2:20pm
CHEM 604G-001 Biochemistry: Metabolism MWF 1:30pm-2:20pm
CHEM 932-001 Advanced Seminar in Biochemistry No Meeting Pattern

Research Interests

My lab mainly studies the biochemistry of viral proteins and small molecules that interact with them in order to discover new antiviral drugs. Our main interest, presently, is in targeting helicases encoded by:

  • The hepatitis C virus (HCV)
  • Dengue virus (DENV)
  • West Nile Virus
  • SARS-CoV-2 (the virus causing COVID-19)

Helicases are motor proteins that separate DNA and RNA duplexes and dislodge proteins bound to nucleic acids in reactions fueled by ATP hydrolysis. We also study helicases from human cells, and other viral proteins as drug targets including polymerases, proteases and capsid proteins. The goal of most projects in the lab is either to understand how these proteins help copy viral genomes or to understand how small molecule drugs block virus growth by directly interfering with these important enzymes.

A molecular model of a fluorescent NS3 helicase inhibitor bound to the protein overlaid on a picture of human cells infected with HCV. The human cells also contain the helicase inhibitor, which is visualized in the cytoplasm using fluorescence microscopy Techniques used in our lab:

    • Recombinant DNA technology
    • Protein purification
    • Enzymology
    • Steady state and transient state kinetics
    • Tissue Culture
    • Fluorescence Microscopy
    • Quantitative RT-PCR
    • High throughput screening
    • Absorbance spectroscopy
    • Fluorescence spectroscopy
    • TR-FRET, alpha-screen and FP assays
    • Biocalorimetry
    • Molecular Modeling

Selected Publications

Ralfs, P., Bressanelli, S., Günter, L. M., Gabel, A., Rothhaar, P., Price, K. J., Tubiana, T., Munschauer, M., Frick, D. N., and Lohmann, V. (2025) Hepatitis C virus NS3 helicase contributes to (-) strand RNA synthesis. Nat. Commun. 16, 8006. PMC12391449  
Frick, D. N., Shittu, M., Bock, C. R., Wardle, Z. P., Rauf, A. A., Ramos, J. N., Thomson, J. G., Sheibley, D. J. and O’Handley, S. F. (2025) Optimization of a High Throughput Screening Platform to Identify Inhibitors of Asymmetric Diadenosine Polyphosphatases. Analytical Biochemistry 115713.
Frick, D. N., Bavisotto, R. V., Hopper, N. C. and Tysoe, W. T. (2025) Analogs of NIH Molecular Probe ML283 Are Potent SARS-CoV-2 Helicase Inhibitors. ACS Chem. Biol. 20, 281-296.   
Zhang, Q., Ali, T., Ponnamperumage, T. N. F., Lin, Z., Setu, N. I., Awoyera, W. O., Oddiri, R. T., Rasmussen, A. D., Felli, M. C., Frick, D. N. and Peng, X. (2025) A Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line. Chem Res Toxicol 38, 216-228. 
Rahman, A. F. M. T., Bulbule, S., Belayet, J. B., Benko, A., Gottschalk, C. G., Frick, D. N., Arnold, L. A., Hossain, M. M. and Roy, A. (2024) JRM-28, a Novel HDAC2 Inhibitor, Upregulates Plasticity-Associated Proteins in Hippocampal Neurons and Enhances Morphological Plasticity via Activation of CREB: Implications for Alzheimer’s Disease. Cells 13, 1964. 
Belayet, J. B., Beamish, S., Rahaman, M., Alanani, S., Virdi, R. S., Frick, D. N., Rahman, A. F. M. T., Ulicki, J. S., Biswas, S., Arnold, L. A., Roni, M. S. R., Cheng, E. Y., Steeber, D. A., Frick, K. M. and Hossain, M. M. (2022) Development of a Novel, Small-Molecule Brain-Penetrant Histone Deacetylase Inhibitor That Enhances Spatial Memory Formation in Mice. J Med Chem 65, 3388-3403. 
Frick, D. N. (2021) A transplant recipient’s pandemic perspective. Transpl Infect Dis; 23:13738.
Virdi, R S., Bavisotto, R V., Hopper, N C., Vuksanovic, N, Melkonian, T R., Silvaggi, Nicholas R., and Frick, David N.“Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3” SLAS discovery : advancing life sciences R & D25.10 (2020): 1162-1170.
Frick, David N., Virdi, R S., Vuksanovic, N, Dahal, N, and Silvaggi, Nicholas R.“Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3” Biochemistry59.28 (2020): 2608-2615.
Ray, A, and Frick, David N.“Fluorescent probe displacement assays reveal unique nucleic acid binding properties of human nudix enzymes” Analytical biochemistry595. (2020): 113622.
Corby, M J., Raicu, Valerica, and Frick, David N.“New Techniques to Study Intracellular Receptors in Living Cells: Insights Into RIG-I-Like Receptor Signaling” Advances in experimental medicine and biology1111. (2019): 219-240.
Yerukhimovich, M M., Marohnic, C C., and Frick, David N.“Role of the Conserved DECH-Box Cysteine in Coupling Hepatitis C Virus Helicase-Catalyzed ATP Hydrolysis to RNA Unwinding” Biochemistry57.43 (2018): 6247-6255.
Corby, M J., Stoneman, M R., Biener, G, Paprocki, J D., Kolli, R, Raicu, Valerica, and Frick, David N.“Quantitative microspectroscopic imaging reveals viral and cellular RNA helicase interactions in live cells” The Journal of biological chemistry292.27 (2017): 11165-11177.
Bassetto, M, Leyssen, P, Neyts, J, Yerukhimovich, M M., Frick, David N., and Brancale, A. “Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication” European journal of medicinal chemistry123. (2016): 31-47.
Bassetto, M, Ferla, S, Leyssen, P, Neyts, J, Yerukhimovich, M M., Frick, David N., O'Donnell, R, and Brancale, A. “Novel symmetrical phenylenediamines as potential anti-hepatitis C virus agents” Antiviral chemistry & chemotherapy(2016).
Bassetto, M, Leyssen, P, Neyts, J, Yerukhimovich, M M., Frick, David N., Courtney-Smith, M, and Brancale, A. “In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase” European journal of medicinal chemistry125. (2016): 1115-1131.
Kaushik-Basu, N, Ratmanova, N K., Manvar, D, Belov, D S., Cevik, O, Basu, A, Yerukhimovich, M M., Lukyanenko, E R., Andreev, I A., Belov, G M., Manfroni, G, Cecchetti, V, Frick, David N., Kurkin, A V., Altieri, A, and Barreca, M L.“Bicyclic octahydrocyclohepta[b]pyrrol-4(1H)one derivatives as novel selective anti-hepatitis C virus agents” European journal of medicinal chemistry122. (2016): 319-25.
Sweeney, Noreena L., Alicia, Hanson M., Mukherjee, Sourav, Ndjomou, Jean, Geiss, Brian J., Steel, John J., Li, Kelin, Frankowski, Kevin J., Schoenen, Frank J., and Frick, David N.“Benzothiazole and Pyrrolone Flavivirus Inhibitors Targeting the Viral Helicase” ACS Infect. Dis1. (2015): 140-148.
Provazzi, P J., Mukherjee, S, Hanson, A M., Nogueira, M L., Carneiro, B M., Frick, David N., and Rahal, P. “Analysis of the Enzymatic Activity of an NS3 Helicase Genotype 3a Variant Sequence Obtained from a Relapse Patient” PloS one10.12 (2015): e0144638.
Ndjomou, Jean, Corby, M. J., Sweeney, Noreena L., Hanson, Alicia M., Aydin, Cihan, Ali, Akbar, Schiffer, Celia A., Li, Kelin, Frankowski, Kevin J., Schoenen, Frank J., and Frick, David N.“Simultaneously Targeting the NS3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy” ACS Chem. Biol10. (2015).

UWM Land Acknowledgement: We acknowledge in Milwaukee that we are on traditional Potawatomi, Ho-Chunk and Menominee homeland along the southwest shores of Michigami, North America’s largest system of freshwater lakes, where the Milwaukee, Menominee and Kinnickinnic rivers meet and the people of Wisconsin’s sovereign Anishinaabe, Ho-Chunk, Menominee, Oneida and Mohican nations remain present.   |   To learn more, visit the Electa Quinney Institute website.