Iminosugars: a host-targeted approach to combat Flaviviridae infections.

Iminosugars: a host-targeted approach to combat Flaviviridae infections.
Antiviral Res. 2020 Aug 05;:104881
Authors: DeWald LE, Starr C, Butters T, Treston A, Warfield KL
Abstract
N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and viral proteins. As viruses lack their own glycosylation machinery, they are dependent on the host's machinery for these processes. Certain iminosugars are known to interfere with the N-linked glycosylation pathway by targeting and inhibiting α-glucosidases I and II in the endoplasmic reticulum (ER). Perturbing ER α-glucosidase function can prevent these enzymes from removing terminal glucose residues on N-linked glycans, interrupting the interaction between viral glycoproteins and host chaperone proteins that is necessary for proper folding of the viral protein. Iminosugars have demonstrated broad-spectrum antiviral activity in vitro and in vivo against multiple viruses. This review discuses the broad activity of iminosugars against Flaviviridae. Iminosugars have shown favorable activity against multiple members of the Flaviviridae family in vitro and in murine models of disease, although the activity and mechanism of inhibition can be virus specific. While iminosugars are not currently approved for the treatment of viral infections, their potential use as future host-targeted antiviral (HTAV...

Source: Antiviral Research - August 4, 2020 Category: Virology Authors: DeWald LE, Starr C, Butters T, Treston A, Warfield KL Tags: Antiviral Res Source Type: research