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Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from <i>Aeromonas hydrophila</i> (<i>Ah</i>PNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a &#8220;one-pot, one-enzyme&#8222; transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2&#8242;-deoxy counterpart were synthesized and incubated either with the &#8220;purine-like&#8222; base or the modified purine of the three selected APIs. Good conversions (49&#8211;67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-<i>N</i>⁶-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of <i>Ah</i>PNP.