Artificial Intelligence Reveals Nature: Functional Parallels Between a Designed and a Natural Peptide

Natural peptides derived from plants have been an important source of medical substances for several decades. Due to their mechanism of action, chemical potential, and favourable side effect profile, these peptides represent a safer alternative to synthetic pharmaceutical treatments. In this study, we report the discovery of a natural peptide derived from the Brassica napus (Canola) proteome that exhibits high functional similarity to an artificial intelligence (AI)-generated peptide that is designed to bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike 1 (S1) protein receptor-binding domain (RBD) region. The results of a series of experiments including molecular docking simulations, as well as binding and inhibition assays suggest that the natural peptide exhibits functions similar to those of the AI-generated peptide in binding to the RBD region and disrupting its interaction with the human host receptor angiotensin-converting enzyme 2 (ACE2). This study demonstrates the potential of AI-designed peptides to facilitate the identification of natural peptides with similar functional properties.