Epi-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses DOI Creative Commons
Melissa Thaler, Tim P. Ofman, Ken Kok

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(8), P. 1594 - 1608

Published: July 25, 2024

The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication a broad range viruses that rely on ER protein quality control. We found, by screening panel deoxynojirimycin cyclitol glycomimetics, the mechanism-based α-glucosidase inhibitor, 1,6-epi-cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 in lung epithelial cells, halting intracellular generation mature spike protein, reducing production infectious progeny, leading reduced syncytium formation. Through activity-based profiling, we confirmed primary airway grown at air–liquid interface. 1,6-epi-Cyclophellitol cyclosulfate inhibits early pandemic more recent variants, as well SARS-CoV MERS-CoV. reported antiviral activity is comparable best-in-class described glucosidase inhibitors, all competitive inhibitors also targeting other glycoprocessing enzymes not involved propose selective blocking ER-resident covalent irreversible manner new strategy search for effective agents

Language: Английский

Epi-Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses DOI Creative Commons
Melissa Thaler, Tim P. Ofman, Ken Kok

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(8), P. 1594 - 1608

Published: July 25, 2024

The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication a broad range viruses that rely on ER protein quality control. We found, by screening panel deoxynojirimycin cyclitol glycomimetics, the mechanism-based α-glucosidase inhibitor, 1,6-epi-cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 in lung epithelial cells, halting intracellular generation mature spike protein, reducing production infectious progeny, leading reduced syncytium formation. Through activity-based profiling, we confirmed primary airway grown at air–liquid interface. 1,6-epi-Cyclophellitol cyclosulfate inhibits early pandemic more recent variants, as well SARS-CoV MERS-CoV. reported antiviral activity is comparable best-in-class described glucosidase inhibitors, all competitive inhibitors also targeting other glycoprocessing enzymes not involved propose selective blocking ER-resident covalent irreversible manner new strategy search for effective agents

Language: Английский

Citations

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