SARS-CoV-2 spike protein-, main protease- and papain-like-protease-targeting peptides from seed proteins following gastrointestinal digestion: An in silico study

BACKGROUND: The anti-COVID-19 potential of phytochemicals was investigated in numerous studies, but efficacy of peptides released by seed proteins upon gastrointestinal (GI) digestion is underexplored. PURPOSE: This study investigated whether multi-target anti-COVID-19 peptides could be released from edible seeds following GI digestion, by using in silico and molecular docking approaches. METHODS: Nineteen seed storage proteins from Chenopodium quinoa (quinoa), Sesamum indicum (sesame), Brassica napus (rape), Helianthus annuus (sunflower) and Cucurbita maxima (pumpkin) seeds were subjected to in silico GI digestion, in order to detect the released peptides with high GI absorption that concurrently target the spike protein, main protease and papain-like protease of SARS-CoV-2. RESULTS: Molecular docking study revealed that 36 peptides with high GI absorption, out of the 1593 peptides released from seed proteins, could bind to the binding or catalytic sites of the spike protein, main protease and papain-like protease of SARS-CoV-2, after GI digestion. Among the five seeds, quinoa was predicted to release the largest number (27) of multi-target peptides. When compared with PIY (Pro-Ile-Tyr), a high-GI-absorption fragment released from a potential anti-COVID-19 peptide, pumpkin-derived peptide PW (Pro-Trp) could bind more strongly to SARS-CoV-2 spike protein. PW was superior to some previously reported anti-SARS-CoV-2 phytochemicals when binding affinities towards the three viral targets were compared. CONCLUSION: Edible seeds are a potential source of anti-COVID-19 peptides upon GI digestion, hence they should be considered as an alternative to assist in the treatment and management of COVID-19.