Modified Nucleosides “(ProTide)” as Potential Anti-HCV Therapeutics

Abstract

Hepatitis C virus (HCV) is among the most common causes of cirrhosis and chronic liver disease worldwide. As a result, many researchers are interested in designing and synthesis of a clinical treatment for HCV. Nucleoside monophosphates and monophosphonates play such an important role for treatments of incurable diseases such as hepatitis. For example, 2'-C-methyladenosine and 2'-C-methyl guanosine have shown activities against HCV in the replicon assay as well as against several members of the flavivirus family. However, their development as drug molecules has been hindered by the inherent poor drug-like properties of the monophosphate and monophosphonate groups. These groups have low bioavailability due to the inefficient cellular uptake, poor in vivo stability and poor intracellular metabolism; the latter drawback being most relevant to monophosphates than monophosphonates. These limitations can be addressed by using por Tide strategy, which is able to help the nucleoside monophosphate delivered inside the cell. In this review, we have discussed the different keys monophosphate and monophosphonate nucleoside prodrugs that has entered clinical development. In addition, the role of the ProTide technology is highlighted for the success in the discovery of nucleoside therapeutics.

Keywords: Hepatitis C, antiviral, nucleoside, ProTide, monophosphates

Cite this Article

Elsharif NA, Dakeel O. Review Article about Modified Nucleosides "(ProTide)" as Potential Anti-HCV Therapeutics. Research and Reviews: A Journal of Pharmaceutical Science. 2017; 8(1): 32–39p.