Uma Singh, Ph.D.

Pharmaceutical and Biomedical Sciences
Assistant Research Scientist
Drug Discovery Group

Pharmaceutical and Biomedical Sciences

Education

Post-Doctoral Associate (with David Chu), Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, 2009-2013

Ph.D. (Organic Medicinal Chemistry), Central Drug Research Institute, India,  2012

 

Areas of Expertise

Drug discovery, design and development

Affiliations
  • Member of International Society for Nucleosides, Nucleotides and Nucleic Acids
  • Member of American Association for the Advancement of Sciences (AAAS)
  • Member of International Society for Anti-viral Research (ISAR)
  • Member of American Chemical Society
Course Instruction

Medicinal Chemistry, PMCY 4300/6300, spring

Pharmaceutical Techniques, PMCY 3300L, spring (Application of NMR, IR and UV in drug discovery and development)

Research Interests
  • Contribute to structures-based drug design and drug discovery.
  • Design and synthesis of nucleosides, nucleotides, and prodrugs as antiviral agents (SARS-CoV-2 (COVID-19), MERS-CoV, HIV, hepatitis B & C virus; West Nile virus, VZV and Epstein–Barr virus).
  • Cancer chemotherapy, design, and synthesis of anti-cancer compounds.
  • Antiviral drug discovery for bioterrorism (Smallpox, Monkeypox, Ebola virus, etc.)
  • Carbohydrate and Nucleoside chemistry.
  • Organic Synthesis/Medicinal Chemistry: Asymmetric Synthesis/ Asymmetric Catalysis.
  • Synthesis of heterocyclic compounds of pharmacological interest.
  • Development of new synthetic methodologies, reactions, and reagents.

Ongoing Research Projects

We are an organic medicinal chemistry group and intend in the drug design, discovery, and development. Our research goal is focused on the development of the new antiviral agents for the pre-clinical and clinical drug candidates. We are developing the new nucleoside and nucleotide analogs, targeting the viral polymerases enzymes against the SARS-CoV-1 & 2 (Severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), hepatitis C virus (HCV), hepatitis B virus (HBV), varicella-zoster virus (VZV), and influenza viruses. In this effort, FMCAP (2′-Fluoro-6′-methylenecarbocyclic Adenosine Phosphoramidate) is developed as a pre-clinical candidate against drug-resistant hepatitis B virus. Another pre-clinical candidate L-BHDU (2-bromovinyl-2-(hydroxymethyl)-1,3 dioxolan uracil) has been developed for the treatment of Shingles.

The outbreak of coronaviruses (CoVs) like SARS-CoV-1 & 2 and MERS-CoV is a severe threat to human health and wealth. Whenever viruses threatened human health, our group has been at the forefront of the discovery of antiviral agents. Against COVID-19 life-threatening situations, our group is involved in the design, synthesis, and development of the novel nucleoside/nucleotide analogs and its prodrugs, targeting the RNA dependent RNA polymerase (RdRp), which is an essential enzyme for viral replication. Hence, RdRp is a unique target for antiviral agents, especially for the nucleoside/nucleotide, which mimics the activity of this enzyme and impede viral replication and transmission.

Selected Publications

Singh, U. S., Chu, C. K. “Synthesis of 2′-deoxy-2′-fluoro-2′-C-methyl spiro cyclopentyl carbocyclic uridine analog as potential inhibitors of HCV NS5B polymerase”. Nucleosides Nucleotides Nucleic Acids 2020, 39 (1-3), 52-68. 

De, C., Liu, D., Singh, U. S., Chu, CK, Moffat, J. F. “β-L-1-[5-(E-2-Bromovinyl)-2-(Hydroxymethyl)-1,3 Dioxolan-4-yl)] Uracil (L-BHDU) Inhibits Varicella Zoster Virus Replication by Depleting the Cellular dTTP Pool”. bioRxiv, 2020. DOI: 10.1101/2020.02.13.948216

Singh, U. S., Mulamoottil, V. A., Chu, C. K. “Synthesis of an Anti-hepatitis B Agent, 2′-Fluoro-6′-methylene-carbocyclic Adenosine (FMCA) and Its Phosphoramidate (FMCAP). J. Org. Chem. 2019, 84 (2), 752-759. 

Singh, U. S., Mulamoottil, V. A., Chu, C. K. “2′-Fluoro-6′-methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti-HBV agent, active against drug-resistant HBV mutants”. Med. Res. Rev. 2018, 38 (3), 977-1002.

Zeybel, M., Luli, S., Sabater, L., Hardy, T., Oakley, F., Leslie, J., Page, A., Salvador, E. M.,   Sharkey, V., Tsukamoto, H., Chu, C. K., Singh, U. S., Ponzoni, M., Perri, P., Di Paolo, D.,  Mendivil, E. J., Mann, J., Mann, D. A. “A Proof-of-Concept for Epigenetic Therapy of Tissue Fibrosis: Inhibition of Liver Fibrosis Progression by 3-Deazaneplanocin A”. Mol. Ther. 2017, 25 (1), 218-231.

Shankar, R., Rawal, R. K., Singh, U. S., Chaudhary, P., Konwar, R., Hajela, K. “Design, synthesis and biological evaluation of hydrazone derivatives as anti-proliferative agents”. Med. Chem. Res. 2017, 26 (7), 1459-1468.

Singh, U. S., Mishra, R. C., Shankar, R., Chu, C. K., “Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam. J. Org. Chem. 2014, 79 (9), 3917-3923.

De, C., Liu, D. M., Zheng, B., Singh, U. S., Chavre, S., White, C., Arnold, R. D., Hagen, F. K., Chu, C. K., Moffat, J. F., “beta-L-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (L-BHDU) prevents varicella-zoster virus replication in a SCID-Hu mouse model and does not interfere with 5-fluorouracil catabolism”. Antivir. Res. 2014, 110, 10-19.

Coen, N., Singh, U., Vuyyuru, V., Van den Oord, J. J., Balzarini, J., Duraffour, S., Snoeck, R., Cheng, Y. C., Chu, C. K., Andrei, G. “Activity and Mechanism of Action of HDVD, a Novel Pyrimidine Nucleoside Derivative with High Levels of Selectivity and Potency against Gammaherpesviruses”. J. Virol.  2013, 87 (7), 3839-3851.

Rawal, R. K., Singh, U. S., Chavre, S. N., Wang, J. N., Sugiyama, M., Hung, W., Govindarajan, R., Korba, B., Tanaka, Y., Chu, C. K. “2′-Fluoro-6′-methylene-carbocyclic adenosine phosphoramidate (FMCAP) prodrug: In vitro anti-HBV activity against the lamivudine-entecavir resistant triple mutant and its mechanism of action”. Bioorg. Med. Chem. Lett. 2013, 23 (2), 503-506.

Wang, J. N., Singh, U. S., Rawal, R. K., Sugiyama, M., Yoo, J., Jha, A. K., Scroggin, M., Huang, Z. H.,  Murray, M. G., Govindarajan, R., Tanaka, Y., Korba, B., Chu, C. K. “Antiviral activity of novel 2′-fluoro-6′-methylene-carbocyclic adenosine against wild-type and drug-resistant hepatitis B virus mutants”. Bioorg. Med. Chem. Lett. 2011, 21 (21), 6328-6331.

Shankar, R., Singh, U.S., Shukla, H., Thakur, V., Hajela, K. “A facile one pot synthesis of 4-aroyl-2-pyrones: via nuclliophillic addition of active methylene groups to 1, 2-diaroylacetylenes”. Synth. Comm. 2011, 41, 2738-2746.

Shankar, R., Chakravarti, B., Singh, U. S., Ansari, M. I., Deshpande, S., Dwivedi, S. K. D., Bid, H. K., Konwar, R., Kharkwal, G., Chandra, V., Dwivedi, A., Hajela, K. “Synthesis and biological evaluation of 3,4,6-triaryl-2-pyranones as a potential new class of anti-breast cancer agents”. Bioorg. Med. Chem. 2009, 17 (11), 3847-3856.

Singh, U. S., Shankar, R., Kumar, A., Trivedi, R., Chattopadhyay, N., Shakya, N., Palne, S., Gupta, S., Hajela, K. “Synthesis and biological evaluation of indolyl bisphosphonates as anti-bone resorptive and anti-leishmanial agents”. Bioorg. Med. Chem. 2008, 16 (18), 8482-8491.

Singh, U. S., Shankar, R., Yadav, G. P., Kharkwal, G., Dwivedi, A., Keshri, G., Singh, M. M., Moulik, P. R., Hajela, K. “Synthesis and structure guided evaluation of estrogen agonist and antagonist activities of some new tetrazolyl indole derivatives”. Eur. J. Med. Chem. 2008, 43 (10), 2149-2158.

Shankar, R., Jha, A. K., Singh, U. S., Hajela, K. “An efficient and improved synthesis of 1,5-diketones: versatile conjugate addition of nucleophiles to α, β-unsaturated enones and alkynones”. Tetra. Lett. 2006, 47, 3077-3079.

PATENT:

 Chung Chu and Uma S. Singh: US Patent Serial Number 9,334,273 B1, titled “An efficient and Stereoselective Synthesis of 2ʹ-Fluoro-6ʹ-Methylene-Carbocyclic Adenosine (FMCA)” issued on 05/10/2016. Assigned to University of Georgia Research Foundation, Inc.

Chu, Chung K.; Mulamoottil, Varughese Alexender; Mishra, Ram C.; Singh, Uma Sharan; US Patent,  PCT Int. Appl. (2017), WO 2017176392 A1 20171012 “Synthesis of 2′-​fluoro-​6′-​methylene-​carbocyclic adenosine (FMCA) and 2′-​fluoro-​6′-​methylene-​carbocyclic guanosine (FMCG)” issued on 05/19/2019. Assigned to University of Georgia Research Foundation, Inc.

BOOK CHAPTER

John Wiley & Sons, Inc. Book ChapterSynthesis of Entecavir and its Novel Class of Analogues.” Ravindra K. Rawal, Uma Sharan Singh, Srinivas Gadthula and Chung K. Chu. Current Protocol in Nucleic Acid Chemistry 47:14.7.1-14.7.17. © 2011 by John Wiley & Sons, Inc. (ISBN: 978-0-471-24662-6)

Grant Support

Ongoing Research Support

2016-2022
30CHU03-ROYALTY RESEARCH
Funding Agency: CHU-Royalty Research
Title: “Design and synthesis of fluoro-contaning carbocyclic nucleoside as potential inhibitors of HCV NS5B polymerase”.

2018-2021
30UGAF41-DRUG DISCOVERY RESEARCH
Funding Agency: UGA drug discovery research support fund.
Title: “Phosphoramidate, phosphate and 5′-O-amino acid prodrugs of β-L-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (L-BHDU): Synthesis, anti-VZV activity, cytotoxicity and stability studies”.

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