Nucleoside analogs (NAs), as antiviral drugs, play a significant role in clinical medicine, constituting approximately 50 % of all antiviral therapies in current use. Nucleoside inhibitors function by mimicking the structure of natural nucleosides, integrating themselves into viral genetic material during replication, and subsequently inhibiting the virus's ability to reproduce. They are used to treat a variety of viral infections, including herpes simplex, hepatitis B, and acquired immunodeficiency syndrome (AIDS). This review offers the development and mechanisms of atypical nucleoside antiviral agents that target novel sites on viral polymerase and other antiviral targets of nucleoside molecules, highlighting their significance in response to emerging viral threats like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).