NRTIs function as "prodrugs," meaning they are inactive upon entry and require by host cell kinases to become active triphosphate metabolites. Once activated, their mechanism follows two critical steps:

They compete with endogenous deoxynucleotides (like dTTP or dCTP) for binding to the viral Reverse Transcriptase (RT) enzyme .

Clinically approved NRTIs are frequently used in combination therapies to improve efficacy and reduce the risk of drug resistance. Notable examples include:

The Role and Mechanism of Nucleoside Reverse Transcriptase Inhibitors (NRTIs)