Novel compounds are provided in the form of nucleoside pyrophosphate and triphosphate analogs. In these analogs, the pyrophosphate or triphosphate group is replaced with a moiety that is isosterically and electronically identical thereto, but is hydrolytically and enzymatically more stable. The compounds are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents, metabolic moderators and the like. The invention also provides pharmaceutical compositions containing a compound of the invention as an active agent, and in addition provides methods of treating disease, including viral infections, cancer, bacterial infections, inflammatory and/or autoimmune diseases, and the like, by administering a compound of the invention to a patient in need of such treatment.