The discovery and development of filociclovir for the prevention and treatment of human cytomegalovirus-related disease

Publication date: Available online 12 January 2020Source: Antiviral ResearchAuthor(s): Islam T.M. Hussein, Jennifer Brooks, Terry L. BowlinAbstractHuman cytomegalovirus (HCMV) infections are widespread among the human population. Infection is persistent and mostly asymptomatic, except in immunocompromised individuals, particularly transplant patients, where significant morbidity and mortality can occur. Currently approved drugs for treating HCMV-related disease [including ganciclovir (GCV), valganciclovir (VGCV), cidofovir (CDV) and foscarnet (FOS)] all target the viral DNA polymerase and suffer from dose-limiting toxicity and resistance issues. The most recently approved drug, letermovir (LMV), was approved only for prophylaxis in adult HCMV-seropositive stem cell transplant recipients. Although LMV is highly potent, high-grade resistance mutations in the terminase gene were shown to readily emerge in vitro and in treated patients. Therefore, there is a need for new drugs that can be used for combinatorial therapeutic and/or prophylactic regimens to counteract the emergence of resistant mutants. Filociclovir (FCV), also known as cyclopropavir or MBX-400, is a methylenecyclopropane nucleoside analog, which has successfully completed Phase I safety studies, and is now entering Phase II clinical efficacy studies for the treatment of HCMV-related disease in transplant patients. FCV is 10-fold more active than GCV against HCMV in vitro, and has activity against all human herpesvi...
Source: Antiviral Therapy - Category: Virology Source Type: research