O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Likely Contribute to the Mutational Trajectory in Variants of Concern
Edgar González-Rodríguez, Mia Zol-Hanlon, Ganka Bineva‐Todd, Andrea Marchesi, Mark Skehel, Keira E. Mahoney, Chloë Roustan, Annabel Borg, Lucia Di Vagno, Svend Kjær, Antoni G. Wrobel, D.J. Benton, Philipp Nawrath, Sabine L. Flitsch, Dhira Joshi, Andrés Manuel González‐Ramírez, Katalin A. Wilkinson, Robert J. Wilkinson, Emma Wall, Ramón Hurtado‐Guerrero, Stacy A. Malaker, Benjamin Schumann
Abstract
-acetylgalactosamine did not impact furin activity in synthetic O-glycopeptides, but the presence of sialic acid reduced the furin rate by up to 65%. Similarly, O-glycosylation with a sialylated trisaccharide had a negative impact on TMPRSS2 cleavage. With a chemistry-centered approach, we substantiate O-glycosylation as a major determinant of spike maturation and propose disruption of O-glycosylation as a substantial driving force for VOC evolution.