BARACLUDE® is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It inhibits all three steps in the viral replication process. By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity. Entecavir is used for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was designed to mimic lysophosphatidylcholine to take advantage of natural lipid uptake pathways and to achieve high intracellular concentrations of the active antiviral, with the aim of increasing the effectiveness of TFV against wild-type and mutant HIV. CMX157 demonstrated potential to effectively suppress replication of multiNRTI-resistant (MNR) HIV that cannot be treated with any currently available NRTIs, including TDF. It is in phase II clinical trial for HIV infections in USA and phase Ib portion of the phase I/II trial for Hepatitis B in Thailand (PO).

Cidofovir is an antiviral nucleotide analogue with significant activity against cytomegalovirus (CMV) and other herpesviruses. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.

Penciclovir (DENAVIR®) is a synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Famciclovir (FAMVIR®) is a prodrug form of penciclovir with improved oral bioavailability.

Ribavirin is a synthetic nucleoside analogue, which was first discovered and developed in 1970 by researchers from the International Chemical & Nuclear Corporation (ICN), today known as Valeant Pharmaceuticals. Ribavirin was initially approved for use in humans to treat pediatric respiratory syncytial virus infections (RSV). In cell cultures the inhibitory activity of ribavirin for RSV is selective. The mechanism of action is unknown. Reversal of the in vitro antiviral activity by guanosine or xanthosine suggests ribavirin may act as an analogue of these cellular metabolites. There were no other significant advancements in the treatment of hepatitis C until 1998, when the combination of ribavirin and interferon-alpha gained approval. Clinically, ribavirin showed a small, additive antiviral effect in combination with interferon, but its main effect was dose-dependent prevention of virological relapse. The mechanism by which the combination of ribavirin and an interferon product exerts its effects against the hepatitis C virus has not been fully established. However, it could be thorough the inhibition of inosine monophosphate dehydrogenase (IMPDH), which is the key step in de novo guanine synthesis, a requirement for viral replication.