Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 4′-OR nucleosides of Formula I: or a pharmaceutically acceptable salt thereof, wherein Base, PD, R, Z1, Z2, Z3, and Z4 are as defined herein.