Exam (elaborations)

Antiviral Chemistry & Chemotherapy’s current antiviral agents FactFile (2nd edition): DNA viruses

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Antiviral Chemistry & Chemotherapy’s current antiviral agents FactFile (2nd edition): DNA viruses Hugh J Field1 * and Erik De Clercq2 1Department of Veterinary Medicine, University of Cambridge, Cambridge, UK 2Rega Institute for Medical Research, Leuven, Belgium *Corresponding author: E-m...

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© 2008 International Medical Press 51Antiviral Chemistry & Chemotherapy ’s current antiviral agents FactFile (2nd edition): DNA viruses
Hugh J Field1* and Erik De Clercq2 1Department of Veterinary Medicine, University of Cambridge, Cambridge, UK 2Rega Institute for Medical Research, Leuven, Belgium
*Corresponding author: E-mail: AVCCtracker@intmedpress.com
Although most of the recent attempts to develop new antiviral agents have been focussed on RNA viruses (in particular, HIV and hepatitis C virus), a few new c ompounds are now awaiting their entry into the ﬁeld of DNA v iruses, particularly poxviruses, such as variola virus, because of the bioterrorist context, and herpesviruses, such a s herpes simplex virus and cytomegalovirus, where the market scene has for many years been dominated by acyclovir, pen ciclovir and ganciclovir and their respective orally bioavailable prodrugs: valaciclovir, famciclovir and valganciclo vir. Here, we review the current ‘state of the art’ with old c ompounds ready to rotate off and new compounds eagerly awaiting to appear on the continuously evolving scene of antiviral drug development.
Key to FactFile
StructureSystematic/other names
NotesCompany/Institution
References: xxx,xxxCompound name
Proprietary name
Abbreviation list
BCNA Bicyclic nucleoside analogue CMV cytomegalovirus EBV Epstein–Barr virus FIV feline immunodeﬁciency virus HBV hepatitis B virus HCMV human cytomegalovirus HHV human herpes virus HPV human papillomavirus HSV herpes simplex virus
NRTI nucleoside reverse transcriptase inhibitorNtRTI nucleotide reverse transcriptase inhibitorSIV simian immunodeﬁciency virus VZV varicella-zoster virusAntiviral Chemistry & Chemotherapy 19:51–62 Factﬁle: DNA viruses
© 2008 International Medical Press 52HN
N H2NO
NN
OHO9-(2-Hydroxyethoxymethyl)guanine, acycloguanosine, aciclovir.
Principal target virus : HSV-1, HSV-2, VZV.
Other activities : HCMV, EBV.
Compound class : Acyclic nucleoside analogue.
Clinical stage : Licensed. Patent expired.
The compound is used for the treatment of mucosal, cutaneous and systemic HSV-1 and HSV-2 infections (including HSV encephalitis and genital herpes), an d in VZV infections (including herpes zoster ophthalmicus). It is also used for the prophylaxis of HSV infections (genital herpes) and VZV infections. Extremely safe compound may be used for long-term suppressive therapy. Still regarded as ‘gold standard’ for HSV therapy. Rather poor oral availability; the oral prodrug is valaciclovir.GlaxoSmithKline (GSK)
References: 1–3Acyclovir
Zovirax®
N
NN
N
O PO
HO
OHNH29-[2-(Phosphonylmethoxy)ethyl]adenine, PMEA, GS 393. Principal target virus : HBV.
Other activities : HIV-1, HIV-2, HCMV, HSV-1, HSV-2, FIV, SIV.
Compound class : NtRTI (acyclic nucleoside phosphonate).
Used as its oral prodrug, adefovir dipivoxil, in the treatment of chronic HBV infections.Gilead Sciences
References: 1,4,5Adefovir
N O
N
CH3SN
SNH2
OOCH3N-[5-aminosulfonyl)-4-methyl-1,3-thiazol-2yl)-N-methyl-[4-(2-pyridinyl)
phenyl]acetamide.
Principal target virus : HSV-1, HSV-2.
Mode of action : Inhibits HSV helicase-primase complex. Compound class: Thiazolylsulfonamide
Developed originally by Bayer Company. An extremely active and speciﬁc inhibitor of HSV-1 and HSV-2, which has been shown efﬁcacious in a variety of infection models.
Resistance mutations found most frequently in helicase and occasionally in primase genes. Mechanism appears to differ slightly from BILS 22BS.AiCuris
References: 6–8BAY 57-1293

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