Advance of structural modification of nucleosides scaffold

With Remdesivir being approved by FDA as a drug for the treatment of Corona Virus Disease 2019 (COVID-19), nucleoside drugs have once again received widespread attention in the medical community. Herein, we summarized modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides, and their bioactivity rules. 2′-“Ara”-substituted by –F or –CN group, and 3′-“ara” substituted by acetylenyl group can greatly influence their anti-tumor activities. Dideoxy dehydrogenation of 2′,3′-sites can enhance antiviral efficiencies. Acyclic nucleosides and L-type nucleosides mainly represented antiviral capabilities. 5-F Substituted uracil analogues exihibit anti-tumor effects, and the substrates substituted by –I, –CF3, bromovinyl group usually show antiviral activities. The sugar coupled with 1-N of triazolid usually displays anti-tumor efficiencies, while the sugar coupled with 2-N of triazolid mainly represents antiviral activities. The nucleoside analogues assembled by cholesterol, polyethylene glycol, fatty acid and phospholipid would improve their bioavailabilities and bioactivities, or reduce their toxicities. This review mainly summarize the effects of structure modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides on the antiviral/anti-tumor activity. [Display omitted] •Nucleosides scaffold feature were summarized.•-F, –CN and Acetylenyl substituent are favorable for their anti-tumor activity.•Dideoxy dehydrogenation of 2′, 3′-sites could enhance antiviral activity.•Acyclic and L-type nucleosides mainly represented antiviral activity.•C–N Glycosidic bond would affect activity of triazolid nucleoside analogues.