Selwyn J Hurwitz1, Raymond F Schinazi. 1. aLaboratory of Biochemical Pharmacology, Department of Pediatrics, Center for AIDS Research, Emory University School of Medicine, Atlanta, Georgia, USA bVeterans Affairs Medical Center, Decatur, Georgia, USA.
Abstract
PURPOSE OF REVIEW: This review focuses on the chemical and pharmacological rationale behind the development of nucleoside antiviral prodrugs (NAPs). RECENT FINDINGS: Highly efficacious NAPs have been developed that extend and improve the quality of lives of individuals infected with HIV and hepatitis B virus (HBV), herpes viruses, and adenovirus infection in immunocompromised individuals. A very high rate of hepatitis C virus (HCV) cure is now possible using NAPs combined with other direct acting antiviral agents (DAAs). SUMMARY: Prodrug strategies can address the issues of poor oral bioavailability and delivery of active metabolites to the targeted cells. Additionally, NAPs demonstrate potential for improving deficiencies in oral absorption, metabolism, tissue distribution, cellular accumulation, phosphorylation, and overall potency, in addition to diminishing potential for in-vivo selection of resistant viruses. NAPs continue to be the backbone for the treatment of HIV and HBV, herpesviruses, and adenovirus infections because their active forms are potent, have long intracellular half-lives and are relatively safe with high barrier to resistance.
PURPOSE OF REVIEW: This review focuses on the chemical and pharmacological rationale behind the development of nucleoside antiviral prodrugs (NAPs). RECENT FINDINGS: Highly efficacious NAPs have been developed that extend and improve the quality of lives of individuals infected with HIV and hepatitis B virus (HBV), herpes viruses, and adenovirus infection in immunocompromised individuals. A very high rate of hepatitis C virus (HCV) cure is now possible using NAPs combined with other direct acting antiviral agents (DAAs). SUMMARY: Prodrug strategies can address the issues of poor oral bioavailability and delivery of active metabolites to the targeted cells. Additionally, NAPs demonstrate potential for improving deficiencies in oral absorption, metabolism, tissue distribution, cellular accumulation, phosphorylation, and overall potency, in addition to diminishing potential for in-vivo selection of resistant viruses. NAPs continue to be the backbone for the treatment of HIV and HBV, herpesviruses, and adenovirus infections because their active forms are potent, have long intracellular half-lives and are relatively safe with high barrier to resistance.
Authors: Nadine G Rouphael; Selwyn J Hurwitz; Mari Hart; Allison Beck; Evan J Anderson; Gregory Deye; Blaire Osborn; Shu Yi Cai; Chris Focht; Cyrille Amegashie; Terry L Bowlin; Jennifer Brooks; Mark J Mulligan Journal: Antimicrob Agents Chemother Date: 2019-08-23 Impact factor: 5.938
Authors: Joseph A Hollenbaugh; Jadd Shelton; Sijia Tao; Sheida Amiralaei; Peng Liu; Xiao Lu; Russell W Goetze; Longhu Zhou; James H Nettles; Raymond F Schinazi; Baek Kim Journal: PLoS One Date: 2017-01-03 Impact factor: 3.240