NOVEL IMINO SUGAR DERIVATIVES DEMONSTRATE POTENT ANTIVIRAL ACTIVITY AND REDUCED TOXICITY

摘要

lmino sugars, such as deoxynoj?rimycin(DNJ), are glucose analogues that selectively inhibit cellular a-glucosidase I and Il (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrwn antiviral activities against many enveloped 5 viruses. In order to develop' imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. Furthermore, these new compounds were shown to be active againstDengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potentant?-DV activity having submicromolar EC50 values and SI of greater than 900. Thesecompounds represent a new generation of iminio sugars and their analogues, having IS application in the clinical treatment of infection ofbv and other members of flavivirdae.