It activates the host unfolded protein response (UPR), counteracting KSHV‐induced inhibition of the protein kinase R‐like endoplasmic reticulum kinase branch, particularly activating transcription factor 4 and C/EBP homologous protein expression. Suppression of N‐glycosylation by the sugar drugs triggers ER stress. Consistently with the higher potency of 2‐DFM, we found thatĭ‐mannose rescues KSHV glycoprotein synthesis and virus production, indicating that inhibition of N‐glycosylation is the main antiviral target usingĭ‐mannose competition experiments. At doses similar to those clinically achievable with 2‐DG, the three drugs impair KSHV replication and virion production in iSLK.219 cells via downregulation of viral structural glycoprotein expression (K8.1 and gB), being 2‐DFM the most potent KSHV inhibitor. Here we compare the antiviral effect of 2‐DG with 2‐fluoro‐deoxy‐ĭ‐glucose, a glycolysis inhibitor, and 2‐deoxy‐fluoro‐ĭ‐mannose (2‐DFM), a specific N‐glycosylation inhibitor. The sugar analog 2‐deoxy‐ĭ‐glucose (2‐DG) is an anticancer agent that is well‐tolerated and safe in patients and was recently demonstrated to be a potent antiviral, including KSHV and severe acute respiratory syndrome coronavirus 2. Because 2‐DG inhibits glycolysis and N‐glycosylation, identifying its molecular targets is challenging. Effective treatments against KS remain to be developed. Kaposi's sarcoma‐associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS), an HIV/AIDS‐associated malignancy.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |