Dual inhibition of HCV and HIV by ring-expanded nucleosides containing the 5:7-fused imidazo[4,5-e][1,3]diazepine ring system. In vitro results and implications

Abstract

Examples of ring-expanded nucleosides (RENs), represented by general structures 1 and 2, exhibited dual anti-HCV and anti-HIV activities in both cell culture systems and the respective target enzyme assays, including HCV NTPase/helicase and human RNA helicase DDX3. Since HCV is a leading co-infection in late stage HIV AIDS patients, often leading to liver cirrhosis and death, the observed dual inhibition of HCV and HIV by the target nucleoside analogues has potentially beneficial implications in treating HIV patients infected with HCV.

Keywords: Antiviral compounds; Dual inhibitors of HCV and HIV; Hepatitis C virus (HCV); Human immunodeficiency virus (HIV); Imidazo[4,5-e][1,3]diazepines; In vitro screening; Inhibition of HCV NTPase/helicase; Inhibition of RNA helicase DDX3; Organic synthesis; Ring-expanded nucleosides.