Glycosylation Modulation Dictates Trafficking and Interaction of SARS-CoV-2 S1 Subunit and ACE2 in Intestinal Epithelial Caco-2 Cells.
Marianne El KhouryDalanda WanesMaura Lynch-MillerAbdullah HoterHassan Y NaimPublished in: Biomolecules (2024)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly targets the upper respiratory tract. It gains entry by interacting with the host cell receptor angiotensin-converting enzyme 2 (ACE2) via its heavily glycosylated spike glycoprotein. SARS-CoV-2 can also affect the gastrointestinal tract. Given the significant role of glycosylation in the life cycle of proteins and the multisystem target of SARS-CoV-2, the role of glycosylation in the interaction of S1 with ACE2 in Caco-2 cells was investigated after modulation of their glycosylation patterns using N -butyldeoxynojirimycin (NB-DNJ) and 1-deoxymannojirimycin (dMM), in addition to mutant CHO cells harboring mutations at different stages of glycosylation. The data show a substantial reduction in the interactions between the altered glycosylation forms of S1 and ACE2 in the presence of NB-DNJ, while varied outcomes resulted from dMM treatment. These results highlight the promising effects of NB-DNJ and its potential use as an off-label drug to treat SARS-CoV-2 infections.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- angiotensin converting enzyme
- induced apoptosis
- angiotensin ii
- cell cycle arrest
- respiratory tract
- coronavirus disease
- oxidative stress
- life cycle
- endoplasmic reticulum stress
- machine learning
- cell death
- emergency department
- type diabetes
- cell proliferation
- bone marrow
- smoking cessation
- combination therapy
- deep learning
- single molecule
- adverse drug