The possibility of biological terrorism has moved from the realm of speculation into reality. This threat can take several forms. One of the most likely pathogens in such a scenario is smallpox. The same characteristics that made smallpox a dreaded human pathogen, including aerosol infectivity and stability outside a human host, make it a potentially devastating biological weapon. Dissemination of smallpox in a major population center could result in the sudden, simultaneous occurrence of thousands of cases of severe illness. The primary reason for this is that so few people are now protected from infection by prior vaccination as a consequence of the declaration in 1980 of the complete eradication of smallpox. Furthermore, vaccination would be of little benefit to persons already infected by terrorist release of the virus and immediate vaccination of the exposed population might not reduce the infectivity of primary cases to prevent secondary transmission. Vaccine availability and quality would also prevent a massive vaccination effort. Because of these limitations, development of chemotherapeutic agents to combat smallpox infection must be undertaken. No such agents currently exist. To address this need, this proposal presents plans for developing drugs that act by inhibiting the enzymes encoded by the smallpox virus upon infection. Focus will be on nucleosides and nucleotides that effect, primarily, nucleic acid metabolism. A consortium of three chemists and two virologists as project leaders, and a virologist consultant, has been put into place for this purpose.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-VSG-M (S1))
Program Officer
Tseng, Christopher K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Auburn University at Auburn
Schools of Arts and Sciences
Auburn University
United States
Zip Code
Das, Subha R; Schneller, Stewart W (2014) The 5'-nor aristeromycin analogues of 5'-deoxy-5'-methylthioadenosine and 5'-deoxy-5'-thiophenyladenosine. Nucleosides Nucleotides Nucleic Acids 33:668-77
Yang, Minmin; Ye, Wei; Schneller, Stewart W (2004) Preparation of carbocyclic S-adenosylazamethionine accompanied by a practical synthesis of (-)-aristeromycin. J Org Chem 69:3993-6
Yin, Xueqiang; Schneller, Stewart W (2004) L-deaza-5'-noraisteromycin. Nucleosides Nucleotides Nucleic Acids 23:67-76
Nair, Vasu; Kamboj, Ramesh C (2003) Inhibition of inosine monophosphate dehydrogenase (IMPDH) by 2-[2-(Z)-fluorovinyl]inosine 5'-monophosphate. Bioorg Med Chem Lett 13:645-7
Rajappan, Vasanthakumar P; Schneller, Stewart W (2003) 5'-Amino-5'-deoxyaristeromycin and its antiviral properties. Bioorg Med Chem 11:5199-201
Chu, C K; Jin, Y H; Baker, R O et al. (2003) Antiviral activity of cyclopentenyl nucleosides against orthopox viruses (Smallpox, monkeypox and cowpox). Bioorg Med Chem Lett 13:9-12
Roy, Atanu; Schneller, Stewart W (2003) 4'- and 1'-methyl-substituted 5'-norcarbanucleosides. J Org Chem 68:9269-73
Jin, Y H; Chu, C K (2003) Practical synthesis of D-cyclopent-2-enone, the key intermediate of carbocyclic nucleosides. Nucleosides Nucleotides Nucleic Acids 22:771-3
Tuncbilek, Meral; Schneller, Stewart W (2003) 9-deaza-5'-noraristeromycin. Bioorg Med Chem 11:3331-4
Jin, Yun H; Liu, Peng; Wang, Jianing et al. (2003) Practical synthesis of D- and l-2-cyclopentenone and their utility for the synthesis of carbocyclic antiviral nucleosides against orthopox viruses (smallpox, monkeypox, and cowpox virus). J Org Chem 68:9012-8

Showing the most recent 10 out of 23 publications