Prospects for adenovirus antivirals

Abstract

Adenoviruses cause a number of self-limiting but often highly infectious diseases that affect multiple organs, most commonly those associated with respiratory, genitourinary and gastrointestinal tracts and the ocular surface. Many factors have driven a search for effective topical and systemic antivirals to adenoviruses. These include patient morbidity, economic losses and chronic visual disturbances associated with epidemic keratoconjunctivitis; and the startling recent trend of high morbidity and rising mortality associated with systemic adenoviral infections in the immunosuppressed, particularly paediatric bone marrow transplant recipients. The development of effective antivirals has proven to be a complex task, owing to the fact that multiple and often genetically divergent adenovirus serotypes can cause similar diseases. Currently, there remains no licensed systemic or topical treatment in the USA or Europe. However, many compounds have been explored for activity against adenoviruses, and some have been evaluated clinically in either a topical setting for ocular disease or in the setting of systemic treatment in the face of life-threatening adenovirus infections. This article outlines such compounds, discusses the potential for their clinical development, and highlights some problems that may be faced in evaluating their efficacy clinically.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…Analysis of HAdV isolates revealed a consistent sensitivity of all types belonging to species C only (224), and the evidence for therapeutic efficacy of the compound in vivo is controversial (225,(230)(231)(232)(233). Ribavirin is therefore not generally recommended for treatment of HAdV infections (143,234). However, despite the conflicting results on the activity against HAdV in vivo, the low nephrotoxicity of ribavirin and the documented in vitro efficacy against HAdV species C may justify its use in specific clinical situations (235,236).…”

Adenovirus DNA Replication

“…All these mutations are located in the AdV Pol-coding region (Kinchington et al 2002). Cidofovir inhibits all HAdV types tested (Kinchington et al 2005). This is in contrast to, for instance, Ribavirin, which inhibits replication in all HAdV-C isolates, but had variable activity in isolates of HAdV-A, B, and D (Morfin et al 2009).…”

Uso de ganciclovir 0,15% gel para tratamento de ceratoconjuntivite adenoviral

“…Não há tratamento específi-co nem profilático para evitar o contágio interhumanos ou a transmissão para o segundo olho do paciente. Alguns agentes como o ganciclovir tem mostrado benefícios potenciais para esta condição (10)(11)(12)(13)(14) e por esta razão foi realizado este estudo. O ganciclovir tópico já é comercializado em vários países da Europa, Ásia, África e América do Sul para tratamento de herpes ocular.…”