Introduction

Human Cytomegalovirus (HMCV) is a ubiquitous beta-herpesvirus that infects from 60% to nearly 80% of the human population worldwide and can cause serious multi-organ infections, such as pneumonia, gastrointestinal diseases and retinitis, which can be fatal in immunosuppressed patients. Additionally, congenital HCMV is associated with neurodevelopmental defects including hearing loss and mental deficits. To date, there are no vaccines available to prevent HCMV infections and no drugs have been approved for the treatment of congenital infections. In addition, the drugs currently in use in adults have low bioavailability, non-negligible toxicity, limited efficacy and are prone to the emergence of drug resistance.

Technical features

This patent protects the use of clinically approved antifungals such as Posaconazole and Isavuconazole alone and / or in combination with antivirals to treat HCMV-associated infections due to their inhibition of the human CYP51 enzyme. In optimization studies, Posaconazole and Isavuconazole also showed efficacy against drug-resistant HCMV strains. Furthermore, the synergistic effect of these antifungals with different anti-HCMV drugs has been demonstrated, paving the way for the future development of new therapeutic combination protocols for the treatment of HCMV infections.

Possible Applications

• Prevention or treatment of drug-resistant human cytomegalovirus-associated infections;
• Treatment of HCMV in combination with antivirals for use in patients including, but not limited, to the immune compromised subjects undergoing hematopoietic stem cell transplantation and pediatric population.

Advantages

• Clinically approved drugs with repurposing potential;
• Effective therapeutic dosage in the same range as in use for fungal infections;
• A broad-spectrum drug: HCMV strain- and host cell line-independent;
• A novel target – host- rather than pathogen-directed approach;
• Overcomes drug resistance to current therapeutics;
• Synergistic with drugs currently in use for treatment of HCMV infection.