The possibility for biological terrorism has moved from the realm of speculation into reality. As a consequence, the National Institute of Allergy and Infectious Diseases has identified a number of agents that pose the greatest threat and has recommended that therapeutic agents be developed against them. Among that group of pathogens are smallpox and the viral hemorrhagic fevers (including the filoviruses Ebola and Marburg). In preparation for possible release of smallpox, plans are well underway to avail sufficient quantities of smallpox vaccine for a large number of people. However, within this population, there are individuals who will not be able to tolerate the vaccine or, for pre-existing health and/or age reasons, will not be suitable to receive vaccine protection. Thus, for these and other reasons, therapeutic agent development has been recommended by the NIAID. This proposal deals with two therapeutic goals in this direction: (i) agents for treating smallpox infection for instances where the vaccine was ineffective, not available or not administered for reasons just outlined, and (ii) drugs to counteract the effects of vaccination when administered. For the filoviruses Ebola and Marburg, which manifest themselves differently than smallpox but still produce horrendous effects, there are currently no pre-infection vaccines nor post-infection therapeutics available. To address these situations, plans are put forth for designing and developing drugs that would act by inhibiting viral replicative steps following infection by these viruses. Focus will be on nucleosides and nucleotides that affect, primarily, nucleic acid metabolism. A consortium of 3 chemists and 10 virologists has been assembled for this purpose. Because of the extensive collaborations that have been ongoing for some time by this group of chemists and virologists, it can be expected that promising anti-orthopoxvirus and anti-filovirus agents will be uncovered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI056540-02
Application #
6785825
Study Section
Special Emphasis Panel (ZAI1-ALR-M (M3))
Program Officer
Tseng, Christopher K
Project Start
2003-08-01
Project End
2008-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
2
Fiscal Year
2004
Total Cost
$1,192,986
Indirect Cost
Name
Auburn University at Auburn
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
066470972
City
Auburn University
State
AL
Country
United States
Zip Code
36849
Ye, Wei; Schneller, Stewart W (2016) The Synthesis of Both Diastereomers of 5'-Methylhomoaristeromycin. Nucleosides Nucleotides Nucleic Acids 35:105-13
Nair, Vasu; Zhang, Fan (2013) Synthesis of a novel carbocyclic analog of bredinin. Molecules 18:11576-85
Yang, Minmin; Ye, Wei; Schneller, Stewart W (2013) 6'-Methyl-5'-homoaristeromycin: a structural variation of the anti-orthopox virus candidate 5'-homoaristeromycin. Bioorg Med Chem 21:4374-7
Liu, Chong; Chen, Qi; Schneller, Stewart W (2012) 3-Bromo-3-deazaneplanocin and 3-bromo-3-deazaaristeromycin: synthesis and antiviral activity. Bioorg Med Chem Lett 22:5182-4
Li, Weikuan; Ye, Wei; Schneller, Stewart W (2012) 6'-Oxa Analogs of S-Adenosylhomocysteine. Tetrahedron 68:65-71
Daffis, Stephane; Szretter, Kristy J; Schriewer, Jill et al. (2010) 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468:452-6
Gowen, Brian B; Wong, Min-Hui; Larson, Deanna et al. (2010) Development of a new tacaribe arenavirus infection model and its use to explore antiviral activity of a novel aristeromycin analog. PLoS One 5:
Rao, Jagadeeshwar R; Jha, Ashok K; Rawal, Ravindra K et al. (2010) (-)-Carbodine: enantiomeric synthesis and in vitro antiviral activity against various strains of influenza virus including H5N1 (avian influenza) and novel 2009 H1N1 (swine flu). Bioorg Med Chem Lett 20:2601-4
Yin, Xue-qiang; Li, Wei-kuan; Yang, Minmin et al. (2009) A new synthesis and an antiviral assessment of the 4'-fluoro derivative of 4'-deoxy-5'-noraristeromycin. Bioorg Med Chem 17:3126-9
Kim, Hyo-Joong; Sharon, Ashoke; Bal, Chandralata et al. (2009) Synthesis and anti-hepatitis B virus and anti-hepatitis C virus activities of 7-deazaneplanocin A analogues in vitro. J Med Chem 52:206-13

Showing the most recent 10 out of 39 publications