Inhibition of host cellular functions required for viral replication is considered another host-targeting antiviral strategy. Extensive pharmacological studies have validated ER glucosidases as valuable host antiviral targets against many enveloped viruses (Chang et al. 2013). Most known ER glucosidase inhibitors are imino sugars like 1-deoxynojirimycin (DNJ) and castanopermine (CAST) derivatives (Taylor et al. 1994).
It is generally believed that inhibition of ER glucosidase I and/or II prevents the removal of the terminal glucose moieties on N-linked glycans and results in misfolding and retention of glycoproteins in the ER and ultimate degradation via the ER-associated degradation (ERAD) pathway (Simsek et al. 2005, Alonzi et al. 2013). As a consequence of the abnormal trafficking and degradation of viral glycoproteins, virion assembly and secretion are inhibited (Chang et al. 2009, Taylor et al. 1998).
Long-term suppression of ER glucosidases I and/or II with more potent inhibitors may cause significant side effects, particularly in nerve and immune systems (Sadat et al. 2014).