Advances and Perspectives in the Management of Varicella-Zoster Virus Infections

Abstract

Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary infection (varicella or chickenpox) followed by establishment of latency in sensory ganglia. The virus can reactivate, causing herpes zoster (HZ, shingles) and leading to significant morbidity but rarely mortality, although in immunocompromised hosts, VZV can cause severe disseminated and occasionally fatal disease. We discuss VZV diseases and the decrease in their incidence due to the introduction of live-attenuated vaccines to prevent varicella or HZ. We also focus on acyclovir, valacyclovir, and famciclovir (FDA approved drugs to treat VZV infections), brivudine (used in some European countries) and amenamevir (a helicase-primase inhibitor, approved in Japan) that augur the beginning of a new era of anti-VZV therapy. Valnivudine hydrochloride (FV-100) and valomaciclovir stearate (in advanced stage of development) and several new molecules potentially good as anti-VZV candidates described during the last year are examined. We reflect on the role of antiviral agents in the treatment of VZV-associated diseases, as a large percentage of the at-risk population is not immunized, and on the limitations of currently FDA-approved anti-VZV drugs. Their low efficacy in controlling HZ pain and post-herpetic neuralgia development, and the need of multiple dosing regimens requiring daily dose adaptation for patients with renal failure urges the development of novel anti-VZV drugs.

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus

“…At large, treatment recommendations for patients with malignancies are consistent with recommendations and guidelines for the general population [19,24,52,[140][141][142][143] as trials specific for patients with malignancies have not been performed. It has to be noticed, though, that brivudin is not approved in the immunocompromised patients and most importantly contraindicated in patients treated with 5-fluoruracil or its prodrugs (like capecitabine, tegafur) due to potential lethal hematologic toxicity [25,38,144]. Further information about treatment in the immunocompromised patient can also be derived from the AGIHO guideline on infections of the central nervous system in patients with hematological disorders [49] and from the S2-consensus-based guideline, referring to patients after solid organ transplantation or allogeneic HSCT [38].…”

Trigeminal Herpes Zoster: A Brief Review

“…Varicella is one of the mildest infections affecting children below 10 years of age, although it can occur at any age (7,10). The lesion begins as pruritic rashes, including maculopapular/pustular eruptions on an erythematous base with various stages of evolution that begins on the trunk and face, which is the hallmark of infection and spreads centrifugally to involve other body areas.…”

Natural Products and Their Derivatives against Human Herpesvirus Infection

“…However, in immunocompromised patients, prolonged treatment with these drugs is more likely to develop drug-resistant strains due to mutations of thymidine nucleoside kinase or DNA polymerase. Recently, there have been some live-attenuated vaccines available for boosting cell-mediated immunity to reduce the incidence of varicella-zoster viral recurrence, but rare side effects are increasingly described due to the increased administration of VZV live vaccines worldwide [37]. No effective herpesvirus vaccine has been found to completely eradicate viral infection due to the occurrence of reactivation until now.…”

“…The chemical structures of twelve miscellaneous compounds possessing antiviral activity are shown in Figure 6. Allicin (37) from fresh garlic extract displayed activity against a wide range of viruses, including enveloped and non-enveloped viruses [93,179]. The antiviral activity of compound 37 and its derivatives was pre-clinical and clinically investigated in a previous Artemisinin-egonol (38) Artemisinin-homoegonol (…”

“…Allicin (37) from fresh garlic extract displayed activity against a wide range of viruses, including enveloped and non-enveloped viruses [93,179]. The antiviral activity of compound 37 and its derivatives was pre-clinical and clinically investigated in a previous review [180].…”