This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Snoeck, R.
Right arrow Articles by Andrei, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Snoeck, R.
Right arrow Articles by Andrei, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2002, p. 3356-3361, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3356-3361.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antivaccinia Activities of Acyclic Nucleoside Phosphonate Derivatives in Epithelial Cells and Organotypic Cultures

R. Snoeck,1* A. Holy,2 C. Dewolf-Peeters,3 J. Van Den Oord,3 E. De Clercq,1 and G. Andrei1

Rega Institute for Medical Research, K.U. Leuven,1 Pathology Department, U.Z. Leuven, B-3000 Leuven, Belgium,3 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Prague 6, Czech Republic2

Received 12 October 2001/ Returned for modification 22 January 2002/ Accepted 17 July 2002

Organotypic "raft" cultures of epithelial cells allow the reconstitution of a skin equivalent that is easily infectible with different viruses with cutaneous tropism. Among these, poxvirus and particularly vaccinia virus (VV) are good candidates for use in antiviral tests, giving histological pictures comparable to those observed in humans infected with smallpox. Therefore, we decided to evaluate a series of phosphonate derivatives for their ability to inhibit VV growth in epithelial cell monolayers, and the most powerful derivatives were tested in the organotypic cultures. The most active compound was 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], followed by 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine, cyclic (S)-HPMPA, 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC; cidofovir, Vistide], and cyclic (S)-HPMPC. Cidofovir, which is on the market for the treatment of human cytomegalovirus retinitis in immunocompromised patients, is potentially a good candidate for the treatment of a poxvirus outbreak, in the absence of any vaccination.

* Corresponding author. Mailing address: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32/16-337341. Fax: 32/16-337340. E-mail: robert.snoeck{at}rega.kuleuven.ac.be.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3356-3361, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3356-3361.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gammon, D. B., Snoeck, R., Fiten, P., Krecmerova, M., Holy, A., De Clercq, E., Opdenakker, G., Evans, D. H., Andrei, G. (2008). Mechanism of Antiviral Drug Resistance of Vaccinia Virus: Identification of Residues in the Viral DNA Polymerase Conferring Differential Resistance to Antipoxvirus Drugs. J. Virol. 82: 12520-12534 [Abstract] [Full Text]  
  • Magee, W. C., Aldern, K. A., Hostetler, K. Y., Evans, D. H. (2008). Cidofovir and (S)-9-[3-Hydroxy-(2-Phosphonomethoxy)Propyl]Adenine Are Highly Effective Inhibitors of Vaccinia Virus DNA Polymerase When Incorporated into the Template Strand. Antimicrob. Agents Chemother. 52: 586-597 [Abstract] [Full Text]  
  • Duraffour, S., Snoeck, R., Krecmerova, M., van Den Oord, J., De Vos, R., Holy, A., Crance, J.-M., Garin, D., De Clercq, E., Andrei, G. (2007). Activities of Several Classes of Acyclic Nucleoside Phosphonates against Camelpox Virus Replication in Different Cell Culture Models. Antimicrob. Agents Chemother. 51: 4410-4419 [Abstract] [Full Text]  
  • Quenelle, D. C., Collins, D. J., Herrod, B. P., Keith, K. A., Trahan, J., Beadle, J. R., Hostetler, K. Y., Kern, E. R. (2007). Effect of Oral Treatment with Hexadecyloxypropyl-[(S)-9-(3-Hydroxy-2- Phosphonylmethoxypropyl)Adenine] [(S)-HPMPA] or Octadecyloxyethyl-(S)-HPMPA on Cowpox or Vaccinia Virus Infections in Mice. Antimicrob. Agents Chemother. 51: 3940-3947 [Abstract] [Full Text]  
  • Lebeau, I., Andrei, G., Dal Pozzo, F., Beadle, J. R., Hostetler, K. Y., De Clercq, E., van den Oord, J., Snoeck, R. (2006). Activities of Alkoxyalkyl Esters of Cidofovir (CDV), Cyclic CDV, and (S)-9-(3-Hydroxy-2-Phosphonylmethoxypropyl)Adenine against Orthopoxviruses in Cell Monolayers and in Organotypic Cultures.. Antimicrob. Agents Chemother. 50: 2525-2529 [Abstract] [Full Text]  
  • Dal Pozzo, F., Andrei, G., Holy, A., Van Den Oord, J., Scagliarini, A., De Clercq, E., Snoeck, R. (2005). Activities of Acyclic Nucleoside Phosphonates against Orf Virus in Human and Ovine Cell Monolayers and Organotypic Ovine Raft Cultures. Antimicrob. Agents Chemother. 49: 4843-4852 [Abstract] [Full Text]  
  • Andrei, G., van den Oord, J., Fiten, P., Opdenakker, G., De Wolf-Peeters, C., De Clercq, E., Snoeck, R. (2005). Organotypic Epithelial Raft Cultures as a Model for Evaluating Compounds against Alphaherpesviruses. Antimicrob. Agents Chemother. 49: 4671-4680 [Abstract] [Full Text]  
  • Keith, K. A., Wan, W. B., Ciesla, S. L., Beadle, J. R., Hostetler, K. Y., Kern, E. R. (2004). Inhibitory Activity of Alkoxyalkyl and Alkyl Esters of Cidofovir and Cyclic Cidofovir against Orthopoxvirus Replication In Vitro. Antimicrob. Agents Chemother. 48: 1869-1871 [Abstract] [Full Text]  
  • Quenelle, D. C., Collins, D. J., Wan, W. B., Beadle, J. R., Hostetler, K. Y., Kern, E. R. (2004). Oral Treatment of Cowpox and Vaccinia Virus Infections in Mice with Ether Lipid Esters of Cidofovir. Antimicrob. Agents Chemother. 48: 404-412 [Abstract] [Full Text]  
  • Keith, K. A., Hitchcock, M. J. M., Lee, W. A., Holy, A., Kern, E. R. (2003). Evaluation of Nucleoside Phosphonates and Their Analogs and Prodrugs for Inhibition of Orthopoxvirus Replication. Antimicrob. Agents Chemother. 47: 2193-2198 [Abstract] [Full Text]  
  • Miravalle, A., Roos, K. L. (2003). Encephalitis Complicating Smallpox Vaccination. Arch Neurol 60: 925-928 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»