Vasu Nair, Ph.D., D.Sc.
CDD Director and Associate Dean for Research, GRA Eminent Scholar
UGA Center for Drug Discovery
|B.S. (with Honors)||University of Otago||Dunedin, New Zealand|
|Ph.D||University of Adelaide||Adelaide, Australia|
|D.Sc. Degree||University of Adelaide||Adelaide, Australia|
- Post-doctoral Experience
- Postdoctoral Research Fellow, Harvard University, Cambridge (with Nobel Laureate R.B. Woodward)
Postdoctoral Associate, University of Illinois, Urbana
- Honors and Awards
- 2008 Inventor of the Year, University of Georgia
Recipient of the Volwiler Award for Outstanding Contributions in Research, AACP, 2007
Georgia Research Alliance Eminent Scholar, 2002-present
Board of Directors, International Society for Antiviral Research, 2003-2007
William Henry Terry, Sr., Chair in Drug Discovery, 2002-present
Head, University of Georgia Department of Pharmaceutical and Biomedical Sciences, 2002-2010
Recipient of the Midwest Award of the American Chemical Society, 2001
Invited Co-Chair, HIV Therapeutics, in “Summit on Development of Infectious Disease Therapeutics,” Bethesda, MD, NIH Conference, 2000
University of Iowa Award for Excellence in Teaching, 1999
Elected Fellow, American Association for the Advancement of Science (AAAS), 1998
Council Member, Gordon Research Conferences, 1998-1999
Editorial Board, Antiviral Chemistry and Chemotherapy, Medicinal Research Reviews, ARKIVOC and Nucleosides, Nucleosides and Nucleic Acids
Mentioned in "2000 Outstanding Scientists of the 20th Century"
Charter Member, AIDS and Related Research Study Section (NIAID), NIH, 1994-98
University of Iowa Foundation Distinguished Professor of Chemistry, 1993-2002
- Research Interests
- Medicinal chemistry, chemical biology and drug discovery, conceptually new compounds with antiviral activities against DNA and RNA viruses including emerging viruses and retroviruses (HIV), molecules with activity against multi-drug resistant tuberculosis.
Research efforts in my laboratory are concerned with the chemistry and biology of nucleosides, nucleotides and related compounds with particular emphasis on the discovery of novel molecules of antiviral therapeutic interest. Application of molecular recognition concepts to viral genes and enzymes form the basis for our drug design work. Chemoenzymatic methods are utilized for the synthesis of new inhibitors targeted at DNA and RNA viruses, including retroviruses such as HIV. Key enzymes of nucleoside and nucleotide metabolism of interest include deaminases, transferases, kinases, phosphodiesterases, and nucleic acid polymerases. Interdisciplinary antiviral studies are performed through national and international collaborative arrangements. One example of success in our quest for new antiviral molecules is the discovery of a compound called an isonucleoside that is potently active against retroviruses (lentiviruses). Its triphosphate is one of the most potent known inhibitors of the viral enzyme, HIV reverse transcriptase. A more recent example of success is the discovery of potent inhibitors of HIV integrase. This viral enzyme is involved in the integration of viral DNA into human DNA, the most devastating step in the attack of human cells by HIV. Blocking the biochemical mechanism of action of this enzyme is a logical approach to preventing this viral DNA invasion of the human system. We have discovered stable (i.e., nuclease-resistant), conceptually-novel dinucleotides (miniature surrogate DNA molecules) that are recognized by wild-type HIV integrase and that have strong inhibitory activity against the viral enzyme. In more recent work, we have designed and synthesized novel molecules constructed on nucleobase scaffolds that inhibit both steps of HIV integrase action. A few of these compounds have been found to exhibit highly potent anti-HIV activity. Other investigations in our laboratory have focused on drug discovery against infectious RNA viruses, with particular emphasis on the virus families, paramyxoviridae, flaviviridae and filoviridae. The enzyme, IMPDH, is used as a probe for RNA antiviral drug discovery. In the last few years, his research has also focused on dual mechanism of active therapeutic agents.
- Representative Publications
- V. Nair, M. Okello, N. Mangu, B. Seo, and M. Gund, A Novel Molecule with Notable Activity Against Multi-drug Resistant Tuberculosis, Bioorganic & Medicinal Chemistry Letters 2015, in press.
V. Nair, M. Okello, S. Mishra, J. Mirsalis, K. O'Loughlin, and Y. Zhong, Pharmacokinetics and Dose-range Finding Toxicity of Novel Anti-HIV Active Integrase Inhibitor, Antiviral Research 2014, 108, 25-29. PMID 24821255.
M. Okello, S. Mishra, M. Nishonov, M. Mankowski, J. D. Russell, J. Wei, P. A. Hogan, R. G. Ptak and V. Nair, A Novel anti-HIV Active Integrase Inhibitor with a Favorable In Vitro Cytochrome P450 and Uridine 5'-diphospho-glucuronosyltransferase Metabolism Profile, Antiviral Res. 2013, 98, 365-372. PMID 23602851.
J. Basca, M. Okello, P. Singh and V Nair, Solid-state Tautomeric Structure and Invariom Refinement of a Novel and Potent Integrase Inhibitor, Acta Cryst. C. 2013, C69, 285-288 (see cover page of March 2013 issue and IUC news release). PMID 23459357.
M. Okello and V. Nair, Invited Chapter, Methodologies for the Synthesis of Isomeric Nucleosides and Nucleotides of Antiviral Significance, in “Chemical Synthesis of Nucleoside Analogues,” P. Merino, Ed., Wiley, 2013, pp 317-344.
B.I. Seo, V.R. Uchil, M. Okello, S. Mishra, X. Ma, M. Nishonov, Q. Shu, G. Chi and V. Nair. Discovery of a Potent HIV Integrase Inhibitor that Leads to a Prodrug with Significant anti-HIV Activity, ACS Med. Chem. Lett. 2011, 2, 877-881. PMID 22328963.
V. Nair and G. Chi. Nucelotide-based Inhibitors of HIV Integrase, in HIV-1 Integrase: Mechanism and Inhibitor Design, Neamati, N., Ed.: Wiley: Hoboken, 2011.
V. Nair, G. Chi, Q. Shu, J. Julander and D. F. Smee, A Heterocyclic Molecule with Significant Activity Against Dengue Virus, Bioorg. Med. Chem. Lett. 2009, 19, 1425-1427. PMID 19185487.
V. Nair and Q. Shu, Inosine Monophosphate Dehydrogenase (IMPDH) as a Target in Drug Discovery, Med. Res. Rev. 2008, 28, 219-232. PMID 17480004.