Irrespective of the particular disease they may cause, all viruses must replicate in order to survive. Drugs that block viral replication, by mimicking the naturally occurring components of RNA or DNA (A,T/U,C,G), are called nucleoside analogs. Nucleoside analogs have three major advantages over other viral inhibitors, which make them the preferred treatment for all infectious diseases for which they are currently available (e.g., HIV, HBV, HCV, HSV, CMV):

• High barrier to resistance

• Broad spectrum of activity

• High efficacy

Their high barrier to resistance correlates with the typically low affinity binding of nucleosides to their target. Their broad spectrum of activity is the result of targeting the viral polymerase active site, which is highly conserved across different viral strains. Their high efficacy is the result of modifying the viral polymerase product – the viral genome – rather than blocking the viral polymerase itself. As nucleoside analogs are incorporated into new viral genomes, they result in defective genomes. In the process, the nucleoside analogs typically have thousands of chances to compromise any single new given viral genome, resulting in their high efficacy. 

Watch the video below to see a nucleoside analog in action.