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Current and potential therapies for the treatment of herpesvirus infections

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Progress in Drug Research

Part of the book series: Progress in Drug Research ((PDR,volume 60))

Summary

Human herpesviruses are found worldwide and are among the most frequent causes of viral infections in immunocompetent as well as in immunocompromised patients. During the past decade and a half a better understanding of the replication and disease-causing state of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), and human cytomegalovirus (HCMV) has been achieved due in part to the development of potent antiviral compounds that target these viruses. While some of these antiviral therapies are considered safe and efficacious (acyclovir, penciclovir), some have toxicities associated with them (ganciclovir and foscarnet). In addition, the increased and prolonged use of these compounds in the clinical setting, especially for the treatment of immunocompromised patients, has led to the emergence of viral resistance against most of these drugs. While resistance is not a serious issue for immunocompetent individuals, it is a real concern for immunocompromised patients, especially those with AIDS and the ones that have undergone organ transplantation. All the currently approved treatments target the viral DNA polymerase. It is clear that new drugs that are more efficacious than the present ones, are not toxic, and target a different viral function would be of great use especially for immunocompromised patients. Here, an overview is provided of the diseases caused by the herpesviruses as well as the replication strategy of the better studied members of this family for which treatments are available. We also discuss the various drugs that have been approved for the treatment of some herpesviruses in terms of structure, mechanism of action, and development of resistance. Finally, we present a discussion of viral targets other than the DNA polymerase, for which new antiviral compounds are being considered.

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Abbreviations

ACV:

9-(2-hydroxyethoxymethyl)guanine (acyclovir)

ACVr :

acyclovir-resistant

BDCRB:

5,6-dichloro-2-bromo-1αD-ribofuranosyl-1H-benzimidazole

BMT:

bone marrow transplant

CDV:

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir)

CMV:

cytomegalovirus

EBV:

Epstein-Barr virus

FCV:

famciclovir

FCVr :

famciclovir-resistant

GCV:

ganciclovir

GCVr :

ganciclovir-resistant

HCMV:

human cytomegalovirus

HPMPC:

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir)

HSV-1:

herpes simplex virus type 1

HSV-2:

herpes simplex virus type 2

IC50 :

inhibitory concentration, 50%

kpb:

kilobase pair

L-FMAU:

the L enantiomer of 2′-fluoro-1-α-D-arabinofuranosyl-5-methyluracil

MP:

monophosphate

ORF:

open reading frame

PCV:

penciclovir

PCVr :

penciclovir-resistant

PFA:

phosphonoformic acid (foscarnet)

PFAr :

foscarnet-resistant

RR:

ribonucleotide reductase

SI:

selective index

TCRB:

2,5,6-trichloro-1-(β-D-ribofuranosyl)benzimidazole

TK:

thymidine kinase

tk:

thymidine kinase gene

TP:

triphosphate

VZV:

varicella zoster virus

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Villarreal, E.C. (2003). Current and potential therapies for the treatment of herpesvirus infections. In: Jucker, E. (eds) Progress in Drug Research. Progress in Drug Research, vol 60. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8012-1_8

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