Mechanism of Action of the Ribopyranoside Benzimidazole GW275175X against Human Cytomegalovirus

Antimicrobial Agents and Chemotherapy

Volumn 48, Issue 5, 2004, Pages 1647-1651

  Underwood, Mark R ^a   Ferris, Robert G ^a   Selleseth, Dean W ^a   Davis, Michelle G ^a   Drach, John C ^b   Townsend, Leroy B ^b   Biron, Karen K ^a   Boyd, F Leslie ^a  

^a GLAXOSMITHKLINE   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 BROMO 5,6 DICHLORO 1 BETA DEXTRO RIBOFURANOSYL 1H BENZIMIDAZOLE; ACICLOVIR; ANTIVIRUS AGENT; BENZIMIDAVIR; BENZIMIDAZOLE DERIVATIVE; CIDOFOVIR; FOMIVIRSEN; FOSCARNET; GW 275175X; IMMEDIATE EARLY PROTEIN; PYRANOSIDE; UNCLASSIFIED DRUG; VALGANCICLOVIR;

ANTIVIRAL ACTIVITY; ARTICLE; BIOAVAILABILITY; CYTOMEGALOVIRUS INFECTION; DNA SYNTHESIS INHIBITION; DRUG MECHANISM; DRUG STABILITY; GENE DELETION; HERPES VIRUS; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; PRIORITY JOURNAL; VIRUS REACTIVATION; VIRUS REPLICATION; VIRUS SHEDDING; VIRUS STRAIN;

ANTIVIRAL AGENTS; BENZIMIDAZOLES; CELL LINE; CYTOMEGALOVIRUS; DNA; ELECTROPHORESIS; HERPESVIRIDAE; HUMANS; IN SITU HYBRIDIZATION; INDICATORS AND REAGENTS; PLAQUE ASSAY; RIBONUCLEOSIDES;

EID: 2142645084     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.48.5.1647-1651.2004     Document Type: Article

References (29)

1. Baldanti, F., M. Underwood, S. Stanat, K. Biron, S. Chou, A. Sarasini, E. Silini, and G. Gerna. 1996. Single amino acid changes in the DNA polymerase confer foscarnet resistance and slow-growth phenotype, while mutations in the UL97-encoded phosphotransferase confer ganciclovir resistance in three double-resistant human cytomegalovirus strains recovered from patients with AIDS. J. Virol. 70:1390-1395.
2. Biron, K., S. Chamberlain, R. Harvey, S. Good, A. Smith, M. Davis, C. Talarico, W. Miller, R. Ferris, R. Dornsife, S. Stanat, J. Drach, L. Townsend, and G. Koszalka. 2002. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob. Agents Chemother. 46:2365-2372.
3. Biron, K., S. Stanat, J. Sorrell, J. Fyfe, P. Keller, C. Lambe, and D. Nelson. 1985. Metabolic activation of the nucleoside analog 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanine in human diploid fibroblasts infected with human cytomegalovirus. Proc. Natl. Acad. Sci. USA 82:2473-2477.
4. Chou, S., N. S. Lurain, K. D. Thompson, R. C. Miner, and W. L. Drew. 2003. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J. Infect. Dis. 188:32-39.
5. Chu, G., D. Vollrath, and R. Davis. 1986. Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science 234:1582-1585.
6. Chulay, J., K. Biron, L. Want, M. Underwood, S. Chamberlain, L. Frick, S. Good, M. Davis, R. Harvey, L. Townsend, J. Drach, and G. Koszalka. 1999. Development of novel benzimidazole riboside compounds for treatment of cytomegalovirus disease, p. 129-134. In J. Mills, P. Volberding, and L. Corey (ed.), Antiviral therapy 5: new directions for clinical applications and research. Kluwer Academic/Plenum Publishers, New York, N.Y.
7. Drew, W., C. Paya, and V. Emery. 2001. Cytomegalovirus (CMV) resistance to antivirals. Am. J. Transplant. 1:307-312.
8. Field, A. 1999. Human cytomegalovirus: challenges, opportunities, and new drug development. Antivir. Chem. Chemother. 10:219-232.
9. Gudmundsson, K., J. Drach, and L. Townsend. 1998. Synthesis of the first C3 ribosylated imidazo[1,2-a]pyridine C-nucleoside by enantioselective construction of the ribose moiety. J. Org. Chem. 63:984-989.
10. Gudmundsson, K., G. Freeman, J. Drach, and L. Townsend. 2000. Synthesis of fluorosugar analogues of 2,5,6-trichloro-1-(β -D-ribofuranosyl)benzimidazole as antivirals with potentially increased glycosidic bond stability. J. Med. Chem. 43:2473-2478.
11. Gudmundsson, K., J. Williams, J. Drach, and L. Townsend. 2003. Synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine C-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran. J. Med. Chem. 46:1449-1455.
12. Hwang, J., and E. Bogner. 2002. ATPase activity of the terminase subunit pUL56 of human cytomegalovirus. J. Biol. Chem. 277:6943-6948.
13. Khare, M., and M. Sharland. 2001. Cytomegalovirus treatment options in immunocompromised patients. Expert Opin. Pharmacother. 2:1247-1257.
14. Koszalka, G., N. Johnson, D. Perkins, S. Good, L. Boyd, S. Chamberlain, and K. Biron. 2002. Preclinical and toxicology studies of 1263W94, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob. Agents Chemother. 46:2373-2380.
15. Krosky, P., M. Baek, and D. Coen. 2003. The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J. Virol. 77:905-914.
16. Krosky, P., K. Borysko, M. Nassiri, R. Devivar, R. Ptak, M. Davis, K. Biron, L. Townsend, and J. Drach. 2002. Phosphorylation of β -D-ribosylbenzimidazoles is not required for activity against human cytomegalovirus. Antimicrob. Agents Chemother. 46:478-486.
17. Krosky, P., M. Underwood, S. Turk, K. Feng, R. Jain, R. Ptak, A. Westerman, K. Biron, L. Townsend, and J. Drach. 1998. Resistance of human cytomegalovirus to benzimidazole ribonucleosides maps to two open reading frames: UL89 and UL56. J. Virol. 72:4721-4758.
18. Roizman, B., and A. Sears. 1996. Herpes simplex viruses and their replication, p. 2231-2295. In B. Fields, D. Knipe, P. Howley, (ed.), Fields virology, 3rd ed., vol. 2. Lippincott-Raven Publishers, Philadelphia, Pa.
19. Scheffczik, H., C. Savva, A. Holzenburg, L. Kolesnikova, and E. Bogner. 2002. The terminase subunits pUL56 and pUL89 of human cytomegalovirus are DNA-metabolizing proteins with toroidal structure. Nucleic Acids Res. 30:1695-1703.
20. Scholz, B., S. Rechter, J. Drach, L. Townsend, and E. Bogner. 2003. Identification of the ATP-binding site in the terminase subunit pUL56 of human cytomegalovirus. Nucleic Acids Res. 31:1426-1433.
21. Sia, I., and R. Patel. 2000. New strategies for prevention and therapy of cytomegalovirus infection and disease in solid-organ transplant recipients. Clin. Microbiol. Rev. 13:83-121.
22. Sullivan, V., K. Biron, C. Talarico, S. Stanat, M. Davis, L. Pozzi, and D. Coen. 1993. A point mutation in the human cytomegalovirus DNA polymerase gene confers resistance to ganciclovir and phosphonylmethoxyalkyl derivatives. Antimicrob. Agents Chemother. 37:19-25.
23. Townsend, L., R. Devivar, S. Turk, M. Nassiri, and J. Drach. 1995. Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-1-(beta-D-ribofuranosyl)benzimidazoles. J. Med. Chem. 38:4098-4105.
24. Townsend, L., J. Drach, S. Good, S. DaLuge, and M. Martin. July 1996. Therapeutic nucleosides. U.S. patent 5,534,535.
25. Townsend, L., K. Gudmundsson, S. Daluge, J. Chen, Z. Zhu, G. Koszalka, L. Boyd, S. Chamberlain, G. Freeman, K. Biron, and J. Drach. 1999. Studies designed to increase the stability and antiviral activity (HCMV) of the active benzimidazole nucleoside, TCRB. Nucleosides Nucleotides 18:509-519.
26. Underwood, M., R. Harvey, S. Stanat, M. Hemphill, T. Miller, J. Drach, L. Townsend, and K. Biron. 1998. Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product. J. Virol. 72:717-725.
27. Vitravene Study Group. 2002. Safety of intravitreous fomivirsen for treatment of cytomegalovirus retinitis in patients with AIDS. Am. J. Ophthalmol. 133:484-498.
28. Williams, S., C. Hartline, N. Kushner, E. Harden, D. Bidanset, J. Drach, L. Townsend, M. Underwood, K. Biron, and E. Kern. 2003. In vitro activities of benzimidazole D- and L-ribonucleosides against herpesviruses. Antimicrob. Agents Chemother. 47:2186-2192.
29. Wolf, D., C. Courcelle, M. Prichard, and E. Mocarski. 2001. Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. USA 98:1895-1900.