PAMS Seminar: "Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor" by Dr. Oliver Grant

PAMS Seminar: "Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor" by Dr. Oliver Grant
Date and time
12:00 PM - 1:00 PM, February 11, 2021
Description

Dr. Oliver Grant

Complex Carbohydrate Research Center
University of Georgia

Note: This seminar is at noon (brown bag seminar)!

Abstract:
Cellular infection by the 2019 severe acute respiratory syndrome coronavirus (SARS-CoV-2) is initiated by binding of the viral spike glycoprotein (S) to its receptor, the angiotensin-converting enzyme 2 (ACE2), which is present on the cellular membrane of human tissues and organs including the lung, intestine and kidney. The SARS-CoV-2 S trimer contains 66 N-linked glycosylation sites, which have been implicated in immune evasion and modulating receptor binding affinity. All sites are occupied by glycans when the spike protein is produced recombinantly in HEK-293 cells, or isolated from virus-derived trimers, or from trimers derived from a viral vectored SARS-CoV-2 vaccine candidate. The human ACE2 (hACE2) receptor contains 6 potential N-linked glycosylation sites that were also found to be occupied under equivalent expression conditions. Recently, we combined a glycoproteomic analysis of the S glycoprotein and hACE2 with molecular dynamics (MD) simulations to generate 3D models of glycosylated hACE2 bound to the S glycoprotein trimer. An analysis of the MD simulations of these 3D structures led to the prediction that ACE2 glycans directly with the S glycoprotein. Thus differences in the occupancy or composition of glycans at these positions may modulate the strength of the S protein - ACE2 interaction, which may in turn impact infectivity, disease severity and transmissibility.

     Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.

This seminar will be held exclusively on Zoom (955 5209 1021). Please visit the Physics Seminars page for a link.

Event sponsor
Admission

Free

Open to public, alumni, current students, faculty, future students, staff
Location
Zoom: 955 2509 1021