New Advances in Short Peptides: Looking Forward.

It is beyond doubt that short peptides hold significant promise in bio-medicine, as the most versatile molecules, both structurally and functionally [...].

A Global Review on Short Peptides: Frontiers and Perspectives.

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

In Silico Identification of Multi-target Anti-SARS-CoV-2 Peptides from Quinoa Seed Proteins.

Peptides are promising antagonists against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). To expedite drug discovery, a computational approach is widely employed for the initial screening of anti-SARS-CoV-2 candidates. This study aimed to investigate the potential of peptides from quinoa seed proteins as multi-target antagonists against SARS-CoV-2 spike glycoprotein receptor-binding domain, main protease, and papain-like protease. Five quinoa proteins were hydrolyzed in silico by papain and subtilisin. Among the 1465 peptides generated, seven could interact stably with the key binding residues and catalytic residues of the viral targets, mainly via hydrogen bonds and hydrophobic interactions. The seven peptides were comparable or superior to previously reported anti-SARS-CoV-2 peptides based on docking scores. Key residues in the seven peptides contributing to binding to viral targets were determined by computational alanine scanning. The seven peptides were predicted in silico to be non-toxic and non-allergenic. The peptides ranged between 546.66 and 3974.87 g/mol in molecular mass, besides exhibiting basic and cationic properties (isoelectric points: 8.26-12.10; net charges: 0.1-4.0). Among the seven peptides, VEDKGMMHQQRMMEKAMNIPRMCGTMQRKCRMS was found to bind the largest number of key residues on the targets. In conclusion, seven putative non-toxic, non-allergenic, multi-target anti-SARS-CoV-2 peptides were identified from quinoa seed proteins. The in vitro and in vivo efficacies of the seven peptides against SARS-CoV-2 deserve attention in future bench-top testing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10214-y.

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.