Our ÄKTA Pure, Ingrid (Bergman, who else), has gotten a little upgrade with a Shimadzu fluorescent detector for those pesky membrane proteins. Over to you, Emma B.
Month: June 2023
Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2
Katherine U. Gaynor, Marina Vaysburd, Maximilian A. J. Harman, Anna Albecka, Phillip Jeffrey, Paul Beswick, Guido Papa, Liuhong Chen, Donna Mallery, Brian McGuinness, Katerine Van Rietschoten, Steven Stanway, Paul Brear, Aleksei Lulla, Katarzyna Ciazynska, Veronica T. Chang, Jo Sharp, Megan Neary, Helen Box, Jo Herriott, Edyta Kijak, Lee Tatham, Eleanor G. Bentley, Parul Sharma, Adam Kirby, Ximeng Han, James P. Stewart, Andrew Owen, John A. G. Briggs, Marko Hyvönen, Michael J. Skynner & Leo C. James
Nature Communications, 14:3583, (2023)
DOI: 10.1038/s41467-023-39158-1
Pubmed: 37328472
PDB coordinates: 8AAA (3D view), 7Z8O (3D view)
Plasmids in Addgene: pExp-His-ZBasic-RBD,
Abstract
COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. Continue reading →