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Chem Biol Drug Des. 2009 Oct;74(4):382-9. doi: 10.1111/j.1747-0285.2009.00874.x. Epub 2009 Aug 19.

Antiherpetic properties of acyclovir 5'-hydrogenphosphonate and the mutation analysis of herpes virus resistant strains.

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1
Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moskvorechie 1, Moscow 115478, Russia.

Abstract

In this study, we continued to study antiherpetic properties of acyclovir 5'-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. Hp-ACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1/L(2) strain. The compound suppressed replication of both ACV-sensitive HSV-1/L(2) and ACV-resistant HSV-1/L(2)/R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1/L(2)/R(Hp-ACV)) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1/L(2)/R(Hp-ACV) population demonstrated their partial cross-resistance to ACV. The mutations determining the resistance of HSV-1 clones to Hp-ACV were partly overlapped with mutations defining ACV resistance but did not always coincide. HSV-1/L(2)/R(Hp-ACV) herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length.

[Indexed for MEDLINE]

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