2018 Volume 30 Issue 176 Pages E139-E145
Antivirals are used to treat viral infections, and antibiotics are used to treat bacterial infections. However, the mechanisms of action and number of commercially available antivirals are very limited compared to those for antibiotics. Accordingly, our group is engaged in ongoing research to develop host-targeting antivirals for the virus infections. This work is primarily focused on the endoplasmic reticulum (ER) glucosidases involved in N-glycan synthesis as the host-dependent factors of viral infection. It is widely accepted that a key mechanism by which those inhibitors act as antivirals is their ability to disrupt virus glycoprotein folding via their inhibition of ER glucosidases. Importantly, very few virus strains are resistant to ER glucosidase inhibitors because ER glucosidase enzymes are not encoded on virus genomes. This avoids problems arising from resistance mutations occurring in the viral target. A number of ER glucosidase inhibitors with antiviral activity have been reported in the past, and several clinical trials of these have been performed. In this paper, we examine the factors preventing the development of these inhibitors as antivirals and our attempts to overcome them.
