SARS-CoV-2 Spike Protein-Derived Cyclic Peptides as Modulators of Spike Interaction with GRP78

Chembiochem. 2024 Apr 13:e202300789. doi: 10.1002/cbic.202300789. Online ahead of print.ABSTRACTThe human glucose-regulated protein GRP78 is a human chaperone that translocactes to the cell surface when cells are under stress. Theoretical studies suggested it could be involved in SARS-CoV-2 virus entry to cells. In this work, we used in vitro surface plasmon resonance-based assays to show that human GRP78 indeed binds to SARS-CoV-2 spike protein. We have designed and synthesised cyclic peptides based on the loop structure of amino acids 480-488 of the SARS-CoV-2 spike protein S1 domain from the Wuhan and Omicron variants and showed that both peptides bind to GRP78. Consistent with the greater infectiousness of the Omicron variant, the Omicron-derived peptide displays slower dissociation from the target protein. Both peptides significantly inhibit the binding of wild-type S1 protein to the human protein GRP78 suggesting that further development of these cyclic peptide motifs may provide a viable route to novel anti-SARS-CoV-2 agents.PMID:38613462 | DOI:10.1002/cbic.202300789

Source: Chembiochem - April 13, 2024 Category: Biochemistry Authors: Nicholas Johnson Craig Pattinson Kate Burgoyne Karolin Hijazi Wael E Houssen Bruce Forbes Milne Source Type: research