Nucleoside analogues are molecules that act like nucleosides in DNA synthesis. They include a range of antiviral products used to prevent viral replication in infected cells. The most commonly used is Acyclovir, although its inclusion in this category is uncertain, as it contains only a partial nucleoside structure, as the sugar ring is replaced by an open-chain structure.
These agents can be used against hepatitis B virus, hepatitis C virus, herpes simplex, and HIV. Once they are phosphorylated, they work as antimetabolites by being similar enough to nucleotides to be incorporated into growing DNA strands; but they act as chain terminators and stop viral DNA Polymerase. They are not specific to viral DNA and also affect mitochondrial DNA. Because of this they have side effects such as bone marrow suppression.
There is a large family of nucleoside analogue reverse transcriptase inhibitors, because DNA production by reverse transcriptase is very different from normal human DNA replication, so it is possible to design nucleoside analogues that are preferentially incorporated by the former. Some nucleoside analogues, however, can function both as NRTIs and polymerase inhibitors for other viruses (e.g., hepatitis B).
Less selective nucleoside analogues are used as chemotherapy agents to treat cancer, eg gemcitabine and 5-FU.
Resistance can develop quickly with as little as one mutation. Mutations occur in the enzymes that phosphorylate the drug to activate it.
Nucleoside analogue drugs include:
Related drugs are nucleobase analogues such as Aciclovir which don't include a sugar, and nucleotide analogues that also include phosphate groups.
See also