Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2
Ross C. Larue, Enming Xing, Adam D. Kenney, Yuexiu Zhang, Jasmine A. Tuazon, Jiànróng Lǐ, Jacob S. Yount, Pui‐Kai Li, Amit Sharma
Abstract
values in the low millimolar range. We identified two peptides that bound Spike RBD in affinity precipitation assays and inhibited infection with genuine SARS-CoV-2. Moreover, these peptides inhibited the replication of a common cold causing coronavirus, which also uses ACE2 as its entry receptor. Results from the infection experiments and modeling of the peptides with Spike RBD identified a 6-amino-acid (Glu37-Gln42) ACE2 motif that is important for SARS-CoV-2 inhibition. Our work demonstrates the feasibility of inhibiting SARS-CoV-2 with peptide-based inhibitors. These findings will allow for the successful development of engineered peptides and peptidomimetic-based compounds for the treatment of COVID-19.