N-Alkyl Derivatives of Deoxynojirimycin (DNJ) as Antiviral Agents: Overview and Update

<i>N</i>-Alkyl deoxynojirimycin-derived drugs, belonging to the class of iminosugars, are well-known for their α-glucosidase inhibitory activity. <i>N</i>-Butyl-deoxynojirimycin (<i>N</i>-butyl-DNJ; NB-DNJ; also known as miglustat or UV-1) has been developed for the treatment of type 1 Gaucher disease and Niemann-Pick disease type C as Zavesca^®. Furthermore, it behaves as a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II (GluI and GluII, respectively) enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; thus, it is a potential antiviral agent. It is studied against a broad range of viruses in vitro and in vivo; however, its utility as antiviral has not been fully explored. Other <i>N</i>-alkylated congeners of DNJ are in preclinical and clinical studies for diverse viral infections. The iminosugar <i>N</i>-9'-methoxynonyl-1-deoxynojirimycin (MON-DNJ or UV-4) is probably the most studied and potent inhibitor of α-Glu I and α-Glu II in clinical trials. It is often studied in the form of its hydrochloride salt (UV-4B) and has broad-spectrum activity against diverse viruses, including dengue and influenza. In clinical trials, it was found to be safe at all doses tested up to 1000 mg. In this paper, an overview on <i>N</i>-alkyl derivatives of DNJ is reported, focusing on their antiviral activity. The literature search was carried out by means of three literature databases, i.e., PubMed/MEDLINE, Google Scholar, and Scopus, screened using different keywords. A brief history of the discovery of their usefulness as antivirals is given, as well as the most recent studies on new compounds belonging to this class. Since different names are often used for the same compound, we tried to dissipate confusion and bring some order to this jumble of names. Specifically, in the tables, all the diverse names used to identify each compound, were reported.