RT Journal Article
SR Electronic
T1 Atypical N-glycosylation of SARS-CoV-2 impairs the efficient binding of Spike-RBM to the human-host receptor hACE2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.09.439154
DO 10.1101/2021.04.09.439154
A1 Gámez, Gustavo
A1 Hermoso, Juan A.
A1 Carrasco-López, César
A1 Gómez-Mejia, Alejandro
A1 Muskus, Carlos E.
A1 Hammerschmidt, Sven
YR 2021
UL http://biorxiv.org/content/early/2021/04/10/2021.04.09.439154.abstract
AB 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. It remains unknown whether atypical N-glycosylation of SGP modulates SARS-CoV-2 tropism for infections. Here, we address this question through an extensive bioinformatics analysis of publicly available structural and genetic data. 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 highly-transmissible mutation N501Y is present in circulating variants of major concerns and affects the SGP-hACE2 binding-interface through the well-known hotspot-353. These findings suggest that atypical SGP post-translational modifications modulate the SGP-hACE2 binding-affinity affecting consequently SARS-CoV-2 transmission and pathogenesis.Competing Interest StatementThe authors have declared no competing interest.