Detection of HSV-1 variants highly resistant to the helicase-primase inhibitor BAY 57-1293 at high frequency in 2 of 10 recent clinical isolates of HSV-1

Journal of Antimicrobial Chemotherapy

Volumn 60, Issue 2, 2007, Pages 274-279

  Biswas, Subhajit ^a   Smith, Christopher ^a   Field, Hugh J ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Antivirals; HSV; Resistance

Indexed keywords

ANTIVIRUS AGENT; BAY 57 1293; HELICASE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CONTROLLED STUDY; FEMALE; GENE SEQUENCE; HERPES SIMPLEX VIRUS 1; HUMAN; HUMAN CELL; MALE; NONHUMAN; NUCLEOTIDE SEQUENCE; VERO CELL; VIRION; VIRUS DETECTION; VIRUS GENE; VIRUS ISOLATION; VIRUS RESISTANCE;

ADULT; AMINO ACID SEQUENCE; ANIMALS; CERCOPITHECUS AETHIOPS; DNA HELICASES; DRUG RESISTANCE, VIRAL; ENZYME INHIBITORS; FEMALE; GENES, VIRAL; HERPES SIMPLEX; HERPESVIRUS 1, HUMAN; HUMANS; MALE; MOLECULAR SEQUENCE DATA; PLAQUE ASSAY; POLYMORPHISM, GENETIC; PYRIDINES; THIAZOLES; VERO CELLS;

EID: 34547837615     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkm182     Document Type: Article

References (15)

1. Kleymann G, Fischer R, Betz UA et al. New helicase - primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 2002; 8: 392-8.
2. Crute JJ, Grygon CA, Hargrave KD et al. Herpes simplex virus helicase - primase inhibitors are active in animal models of human disease. Nat Med 2002; 8: 386-91.
3. Liuzzi M, Kibler P, Bousquet C et al. Isolation and characterization of herpes simplex virus type 1 resistant to aminothiazolylphenyl-based inhibitors of the viral helicase-primase. Antiviral Res 2004; 64: 161-70.
4. Spector FC, Liang L, Giordano H et al. Inhibition of herpes simplex virus replication by a 2-amino thiazole via interactions with the helicase component of the UL5-UL8-UL52 complex. J Virol 1998; 72: 6979-87.
5. Betz UAK, Fischer R, Kleymann G et al. Potent in vivo antiviral activity of the herpes simplex virus primase-helicase inhibitor BAY 57-1293. Antimicrob Agents Chemother 2002; 4: 1766-72.
6. Crumpacker CS, Schaffer PA. New anti-HSV therapeutics target the helicase-primase complex. Nat Med 2002; 8: 327-8.
7. Bacon TH, Levin MJ, Leary JJ et al. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev 2003; 6: 14-28.
8. Biswas S, Swift M, Field HJ. High frequency of spontaneous helicase primase inhibitor (BAY 57-1293) drug-resistant variants in certain laboratory isolates of HSV-1. Antivir Chem Chemother 2007; 18 13-23.
9. McGeoch DJ, Dalrymple MA, Dolan A et al. Structures of the herpes simplex type 1 genes required for virus DNA replication. J Virol 1988; 62: 444-53.
10. Hacker KH, Roux KH. High and low annealing temperatures increase both specificity and yield in touchdown and stepdown PCR. BioTech 1996; 20: 478-85.
11. Zhu L, Weller SK. The six conserved helicase motifs of the UL5 gene product, a component of the herpes simplex virus type 1 helicase primase, are essential for its function. J Virol 1992; 66: 469-79.
12. Kimura M. Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proc Natl Acad Sci USA 1991; 88: 5969-73.
13. Kimura M. The neutral theory of molecular evolution: A review of recent evidence. Jpn J Genet 1991; 66: 367-86.
14. Biswas S, Jennens L, Field HJ. Single amino acid substitutions in the HSV-1 helicase protein that confer resistance to the helicase-primase inhibitor, BAY 57-1293 are associated with increased or decreased virus growth characteristics in tissue culture. Arch Virol [4 April 2007, Epub ahead of print].
15. Biswas S, Jennens L, Field HJ. The helicase primase inhibitor, BAY 57-1293 shows potent therapeutic antiviral activity superior to famciclovir in BALB/c mice infected with herpes simplex virus type 1. Antivir Res 2007; 75: 30-5.