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- Title
Atypical N-glycosylation of SARS-CoV-2 impairs the efficient binding of Spike-RBM to the human host receptor hACE2.
- Authors
Adolfo Gámez, Gustavo; Antonio Hermoso, Juan; Andrés Carrasco-López, César; Gómez-Mejia, Alejandro; Enrique Muskus, Carlos; Hammerschmidt, Sven
- Abstract
Introduction: SARS-CoV-2 internalization by human host cells relies on the molecular binding of its spike glycoprotein (SGP) to the angiotensin-converting-enzyme-2 (hACE2) receptor. Objective: To get insights into the potential role of atypical N-glycosylation sequons of SGP in modulating SARS-CoV-2 tropism for infections. Materials and methods: We made an extensive bioinformatics analysis of publicly available structural and genomic data. Results: We identified two atypical sequons (sequences of N-glycosylation: NGV 481- 483 and NGV 501-503) strategically located on the receptor-binding motif (RBM) of SGP and facing the hACE2 receptor. Interestingly, the cryo-electron microscopy structure of trimeric-SGP in complex with potent-neutralizing antibodies from convalescent patients revealed covalently-linked N-glycans in NGV 481-483 atypical sequons. Furthermore, NGV 501-503 atypical sequon involves the asparagine-501 residue whose highlytransmissible mutation N501Y is present in circulating variants of major concern and affects the SGP-hACE2 binding interface through the well-known hotspot-353. Conclusion: These findings suggest that atypical SGP post-translational modifications modulate the SGP-hACE2 binding-affinity affecting consequently SARS-CoV-2 transmission and pathogenesis.
- Subjects
SARS-CoV-2; POST-translational modification; COVID-19; PATHOGENESIS
- Publication
Biomédica: Revista del Instituto Nacional de Salud, 2021, Vol 41, p160
- ISSN
0120-4157
- Publication type
Article