Phosphonated nucleoside analogues as antiviral agents

The present review is focused on the description of synthesis and antiviral activities of both acyclic and carbocyclic nucleoside phosphonates, endowed with an antiviral potential. Despite the outstanding results in antiviral therapy of acyclovir and azidothymidine, a major drawback concerning the use of nucleoside analogues (NA) is the retention of their stability following triphosphorylation within the host cell. The instability of the phosphate forms of NA has been, at least partially, overcome by the introduction of phosphate groups in the molecular structure. This approach gives rise to two main classes of compounds endowed with ascertained or potential antiviral activity, such as acyclic nucleoside phosphonates (ANP) and phosphonated carbocyclic nucleosides (PCN). Regarding ANP, a higher affinity for HIV reverse transcriptase (RT), with respect to NA, and the potent inhibition of HIV and hepatitis B virus (HBV) have been reported