Diversification of Nucleoside Analogues as Potent Antiviral Drug Leads

Abstract

Nucleoside analogues are potent antiviral agents, but the continuous emergence of pathogenic viruses demands novel and diverse structures. Herein, we have created a diversified library of highly bioactive and non-cytotoxic nucleoside analogues featuring an unprecedented carbobicyclic core that mimics natural ribonucleoside conformation. These regio- and stereo-divergent analogues exhibit up to 16-fold greater antiviral efficacy than the FDA-approved antiviral, ribavirin. Importantly, the carbobicyclic core structure is critical for the potent antiviral efficacy, thus opening up ample opportunities for further lead optimization and mechanistic investigations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/545395v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@fbd078org.highwire.dtl.DTLVardef@3399a9org.highwire.dtl.DTLVardef@1ad5fcborg.highwire.dtl.DTLVardef@16c2f3d_HPS_FORMAT_FIGEXP M_FIG C_FIG