This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Clercq, E Articles by Konno, T Search for Related Content PubMed PubMed Citation Articles by De Clercq, E Articles by Konno, T

 Previous Article  |  Next Article 

Antimicrob Agents Chemother. 1989 August; 33(8): 1291-1297

Broad-spectrum antiviral activities of neplanocin A, 3-deazaneplanocin A, and their 5'-nor derivatives.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

ABSTRACT

The neplanocin A analogs, 3-deazaneplanocin A, 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine (DHCA), and 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (DHCDA), all potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were studied for their broad-spectrum antiviral potential. 3-Deazaneplanocin A, DHCA, and DHCDA proved specifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, and rotavirus. Their selectivity was greater than that of neplanocin A, particularly against vesicular stomatitis virus and rotavirus. As could be expected from adenosine analogs that are directly targeted at AdoHcy hydrolase, 3-deazaneplanocin A, DHCA, and DHCDA were fully active in adenosine kinase-deficient cells, implying that their activity did not depend on phosphorylation by adenosine kinase. None of the AdoHcy hydrolase inhibitors showed selective activity against human immunodeficiency virus (type 1). 3-Deazaneplanocin A at a dose of 0.5 mg/kg per day conferred marked protection against a lethal infection of newborn mice with vesicular stomatitis virus.

This article has been cited by other articles:

• Reddy, M. C.M., Kuppan, G., Shetty, N. D., Owen, J. L., Ioerger, T. R., Sacchettini, J. C. (2008). Crystal structures of Mycobacterium tuberculosis S-adenosyl-L-homocysteine hydrolase in ternary complex with substrate and inhibitors. Protein Sci. 17: 2134-2144 [Abstract] [Full Text]  
• Tan, J., Yang, X., Zhuang, L., Jiang, X., Chen, W., Lee, P. L., Karuturi, R.K. M., Tan, P. B. O., Liu, E. T., Yu, Q. (2007). Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 21: 1050-1063 [Abstract] [Full Text]  
• Hermann, L. L., Coombs, K. M. (2004). Inhibition of Reovirus by Mycophenolic Acid Is Associated with the M1 Genome Segment. J. Virol. 78: 6171-6179 [Abstract] [Full Text]  
• De Clercq, E. (2001). Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections. Clin. Microbiol. Rev. 14: 382-397 [Abstract] [Full Text]  
• De Clercq, E. (2001). Molecular Targets for Antiviral Agents. J. Pharmacol. Exp. Ther. 297: 1-10 [Abstract] [Full Text]  
• Daelemans, D., Esté, J. A., Witvrouw, M., Pannecouque, C., Jonckheere, H., Aquaro, S., Perno, C.-F., Clercq, E. D., Vandamme, A.-M. (1997). S-Adenosylhomocysteine Hydrolase Inhibitors Interfere with the Replication of Human Immunodeficiency Virus Type 1 through Inhibition of the LTR Transactivation. Mol. Pharmacol. 52: 1157-1163 [Abstract] [Full Text]