Michael J Sofia

My research interests include the discovery and development of small molecule and RNA-based therapeutics to treat viral infections and conditions arising from immune system disregulation.

• American Chemical Society
• Royal Society of Chemistry
• Organic Division of the American Chemical Society
• Medicinal Chemistry Division of the American Chemical Society
• American Association for the Advancement of Science
• International Society of Antiviral Research
• American Association for the Study of Liver Disease

1. “Discovery of a b-D-2’-Deoxy-2’-a-Fluoro-2’-b-C-Methyluridine Nucleotide Prodrug (PSI-7977) for the Treatment of Hepatitis C Virus”, M.J. Sofia, D. Bao, W. Chang, J. Du, N. Dhanapalan, S. Rachakonda, G. Reddy, B. Ross, P. Wang, H-R. Zhang, S. Bansal, C. Espiritu, M. Keilman, A. Lam, H. Steuer, C. Niu, M. Otto, P. Furman, J. Med. Chem., 2010, 53, 7202-7218. https://doi.org/10.1021/jm100863x

2. “The Mechanism of Action of b-D-2’-Deoxy-2’-Fluoro-2’-C-Methylcytidine Involves a Second Metabolic Pathway Leading to b-D-Deoxy-2’-Fluoro-2’-C-Methyluridine 5’-Triphosphate, a Potent Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase”, Murakami, E., Niu, C., Bao, H., Steuer, H.M.M., Witaker, T., Nachman, T. Sofia, M.J., Wang, P., Otto, M.J., Furman, P.A., Antimicrobial Agents and Chemotherapy, 2008, 52, 458-464. http://aac.asm.org/content/52/2/458.full.pdf https://journals.asm.org/doi/10.1128/AAC.01184-07

3. “Mechanism of Action of PSI-7851 and Its Diastereoisomer PSI-7977”, E. Murakami, T. Tolstykh, H. Boa, C. Niu, H. Steuer, D. Bao, W. Chang, C. Espiritu, S. Bansal, A. Lam, M. Otto, M.J. Sofia, P. Furman, J. Biol. Chem., 2010, 285, 34337-34347. https://www.ncbi.nlm.nih.gov/pubmed/20801890

4. “Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates”, B. Ross, P.G. Reddy, H-R. Zhang, S. Rachakonda, M.J. Sofia, J. Org. Chem., 2011, 76, 8311-8319. https://www.ncbi.nlm.nih.gov/pubmed/21916475

5. “Structure of HCV Polymerase in Complex with Primer-Template RNA” R. Mosley, T. Edwards, E. Murakami, A. Lam, R. Grice, J. Du, M. J. Sofia, P. Furman, M. Otto, J. Virology, 2012, 86, 6503-6511. https://journals.asm.org/doi/10.1128/jvi.00386-12

6. “Structural Basis for RNA Replication by the Hepatitis C Virus Polymerase”, Appleby, T.C.,

Perry, J., Murakami, E., Barauskas, E., Feng, J., Cho, A, Fox III, D., Wetmore, D.R., McGrath, M., Ray, A., Sofia, M.J., Swaminathan, S, Edwards, T., Science, 2015, 347, 771-775. https://www.ncbi.nlm.nih.gov/pubmed/25678663

7. “Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infections”, W. Chang, D. Bao, B-K. Chun, D. Naduthambi, D. Nagarathnam, S. Rachakonda, P.G. Reddy, B.S. Ross, H-R. Zhang, S. Bansal, C.L. Espiritu, M. Keilman, A. M. Lam, C. Niu, H. M. Steuer, P.A. Furman, M.J. Otto, and M.J. Sofia, ACS Medicinal Chem. Lett., 2011, 2, 130-135.

https://pubs.acs.org/doi/abs/10.1021/ml100209f

8. “2’-Deoxy-2’-a-Fluoro-2’-b-C-Methyl 3’,5’-Cyclic Phosphate Nucleotide Prodrug Analogs as Inhibitors of HCV NS5B Polymerase: Discovery of PSI-352938” P.G. Reddy, D. Bao, W. Chang, B-K. Chun, J. Du, D. Nagarathnam, S. Rachakonda, B.S. Ross, H-R. Zhang, S. Bansal, C.L. Espiritu, M. Keilman, A.M. Lam, C. Niu, H.M. Steuer, P.A. Furman, M.J. Otto, and M.J. Sofia, Bioorg. Med. Chem. Lett., 2010, 20, 7376-7380. https://www.sciencedirect.com/science/article/pii/S0960894X10014861?via%3Dihub

9. “Inhibition of Hepatitis C Virus Replicon by PSI-352938, a Cyclic Phosphate Prodrug of β-D-2’-Deoxy-2’-α-Fluoro-2’-β-C-Methylguanosine”, A. Lam, C. Espiritu, E. Murakami, V. Zennou, S. Bansal, H. Steuer, C. Niu, M. Keilman, H. Bao, N. Bourne, R. Vesele, G.P. Reddy, W. Chang, J. Du, D. Nagarathnam, M.J. Sofia, M.J. Otto, P. Furman, Antimicrob. Agents Chemother., 2011, 55, 2566-2575. https://aac.asm.org/content/55/6/2566

10. “The Use of 2’-Spirocyclic Ethers in HCV Nucleoside Design”, J. Du, B-K Chun, R.T. Mosley, S. Bansal, H. Bao, C. Espiritu, A. M. Lam, E. Murakami, C. Niu, H.M. Steuer, P.A. Furman, M.J. Sofia, J. Med. Chem., 2014, 57, 1826-1835. https://pubs.acs.org/doi/abs/10.1021/jm401224y

11. “Alkyl 3’,5’-Cyclic Phosphate b-D-2’-a-F-2’-b-C-Methyl-2-Amino-6-O-Substituted Purine Nucleotide Prodrugs as Inhibitors of Hepatitis C Virus Replication: A Structure Activity Relationship Study, J. Du, D. Bao, B-K. Chun, Y. Jiang, P.G. Reddy, H-R. Zhang, B.S. Ross, S. Bansal, H. Bao, C. Espiritu, A.M. Lam, E. Murakami, C. Niu, H.M. Steuer, P.A. Furman, M.J. Otto, M.J. Sofia, Bioorg Med Chem Lett., 2012, 22, 5924-5929. https://scholar.google.com/scholar?q=Bioorg+Med+Chem+Lett.,+2012,+22,+5924-5929&hl=en&as_sdt=0&as_vis=1&oi=scholart

12. “Inhibition of HCV NS5A by Fluoro-olefin Based γ-Turn Mimetics” W, Chang, R.T. Mosley, S. Bansal, M. Keilman, A. Lam, P.A. Furman, M. Otto, M.J. Sofia, Bioorg Med Chem Lett., 2011, 22, 2938-2942. https://www.sciencedirect.com/science/article/abs/pii/S0960894X12002430

13. ”Checkpoint Inhibition Through Small Molecule-Induced Internalization of Programmed Death-Ligand 1” Park, J-J., Thi, E., Carpio, V., Bi, Y., Cole, A., Dorsey, B., Fan, K., Harasym, T., Lott, C., Kadhim, S., Kim, J-H., Lee, A., Nguyen, D., Paratala, B., Qiu, R., White, A., Lakshminarasimhan, D., Leo, C., Suto, R., Rijnbrand, R., Tang, S., Sofia, M.J., Moore, C., Nature Comm., 2021, 12, 1222. https://pubmed.ncbi.nlm.nih.gov/33619272/

14. “Control of Chronic Hepatitis B Virus Infection with Imdusiran, a Small Interfering RNA Therapeutic”, Thi, E., Xin, y., Snead, N., Lee, A., Steuer, H., Ardzinski, A., Graves, I., Espiritu, C., Cuconati, A., Abbott, C., Jarosz, A., Teng, X, Paratala, B., McClintock, K., Harasym, T., Rijnbrand, R., Lam, A., Sofia, M.J., ACS Inf. Diseases, 2024, https://doi.org/10.1021/acsinfecdis.4c00514.

15. “Rational Design, Synthesis, and Structure-Activity Relationship of a Novel Isoquinolinone-Based series of HBV Capsid Assembly Modulators Leading to the Identification of Clinical Candidate AB-836”, Cole, A., Kultgen, S., Mani, N., Fan, K., Ardzinski, A., Stever, K., Dorsey, B., Mesaros, E., Thi, E., Graves, I., Tang, S., Harasym, T., Lee, A., Olland, A., Suto, R., Sofia, M.J., J. Med. Chem, 2024, https://doi.org/10.1021/acs.jmedchem.4c01568

Michael J. Sofia, Ph.D. is internationally recognized for his work on the discovery and development of drugs to treat and cure viral diseases including HCV and HBV and is currently a Distinguished Professor at the Baruch S. Blumberg Institute. He was co-founder and Chief Scientific Officer of Arbutus Biopharma, Inc for over 12 years until his retirement in 2024. Over his 38 year career in drug discovery Dr. Sofia has held research and research management positions at Gilead Sciences, Pharmasset, Bristol-Myers Squibb, Transcell Technologies and Eli Lilly and Company.

During his career Dr. Sofia has introduced numerous drugs into clinical development and was responsible for the discovery and early development of sofosbuvir (Sovaldiâ,). Sofosbuvir quickly became the most successful drug launched in history and was designated by the World Health Organization as an essential medicine. Sofosbuvir became the backbone of HCV-cure therapies and is part of the fixed-dose combination regimens Harvoni®, Epclusa® and Vosevi®. In addition, sofosbuvir has been used in combination with many other HCV targeted agents. To date over 10 million individuals have been cured of HCV using sofosbuvir-based therapeutic regimens.

Dr Sofia holds a BA in chemistry from Cornell University, a Ph.D. from the University of Illinois Urbana-Champaign and was an NIH postdoctoral fellow at Columbia University. Michael has published extensively in the area of drug discovery and development and has authored over 135 publications, 17 book chapters, numerous abstracts and edited 3 books on drug discovery topics. He is also an inventor on more than 56 US patents and numerous patent applications. He has been an invited speaker at over 126 national and international conferences and universities. Dr. Sofia sits on several non-profit advisory boards and is a member of the Board of Trustees for St Joseph’s University, Philadelphia PA. He is also on the advisory boards of Chemical & Engineering News, ACS Medicinal Chemistry Letters, and ChemMedChem

For his work in drug discovery, Dr. Sofia has been the recipient of numerous awards. These include the 2014 Pennsylvania Bio Scientific Achievement Award, the 2015 Heroes of Chemistry Award of the American Chemical Society, Foreign Policy Magazine’s 2014 Global Thinkers Award, the Economist Magazine’s 2015 Innovation Award in Biosciences, the 2016 IUPAC-Richter Prize in Medicinal Chemistry, the 2016 Lasker-Debakey Award in Clinical Medical Research, the Gertrude Elion Award from the International Society for Antiviral Research, the 2017 University of Illinois LAS Alumni Achievement Award, the Science and Technology Medal from the New Jersey Research and Development Council, the 2018 International Society of Nucleosides, Nucleotides and Nucleic Acids John Montgomery Award, the 2018 Humanitarian Award by the Sons of Italy in America and the 2019 Pennsylvania Drug Discovery Award from the PA Drug Discovery Institute. In 2020 he was awarded the Cameron Prize for Therapeutics from the University of Edinburgh. In 2019 he received an honorary doctoral degree from the University of Messina, Italy. He was inducted into the ACS Medicinal Chemistry Hall of Fame in 2017 and is a Fellow of the Royal Society of Chemistry.

Dr. Sofia’s research interests include the discovery and development of small molecule and RNA-based therapeutics to treat viral infections and conditions arising from immune system disregulation.