Coronavirus Disease 2019 , an infectious disease caused by SARS-CoV-2, has become the most contagious pandemic in the world. The binding of SARS-CoV-2 spike glycoprotein Receptor-binding Domain (RBD) to human angiotensin-converting enzyme 2 receptor precedes cell entry. Thus, RBD of SARS-CoV-2 spike glycoprotein is a key target for the development of drugs and vaccines to curb COVID-19. The aim of this in silico study was to identify potential SARS-CoV-2 cell entry inhibitors from peptides derived from edible insects. Twenty-four major proteins from mealworms, silkworm cocoons and housefly larvae were subjected to in silico gastrointestinal (GI) digestion, yielding 3560 fragments. Further screening led to 82 high-GI-absorption peptides with unique sequences. Molecular docking revealed 10 promising peptides (VPW, PPY, PIF, VW, PSF, PGF, PAY, VGF, PF and TW), predicted to interact with at least one key binding residue on RBD. Notably, VPW had the lowest docking energy score (−144.359) and binding affinity (−7.0 kcal/mol), highlighting its potency among the ten peptides. Binding affinities of the insect peptides were superior to some reported natural products. Our study suggests that when consumed, edible insects may be a source of putative SARS-CoV-2 cell entry inhibitors in the form of RBD-binding peptides.

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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.

Acute hepatopancreatic necrosis disease (AHPND), caused by PirAvp- and PirBvp-releasing Vibrio parahaemolyticus strains, has resulted in massive mortality in shrimp aquaculture. Excessive use of antibiotics for AHPND management has led to antibiotic resistance, highlighting the urgency to search for alternatives. Using an in silico approach, we aimed to discover PirAvp/PirBvp-binding peptides from oilseed meals as alternatives to antibiotics. To search for peptides that remain intact in the shrimp digestive tract, and therefore would be available for toxin binding, we focused on peptides released from tryptic hydrolysis of 37 major proteins from seeds of hemp, pumpkin, rape, sesame, and sunflower. This yielded 809 peptides. Further screening led to 24 peptides predicted as being non-toxic to shrimp, fish, and humans, with thermal stability and low water solubility. Molecular docking on the 24 peptides revealed six dual-target peptides capable of binding to key regions responsible for complex formation on both PirAvp and PirBvp. The peptides (ISYVVQGMGISGR, LTFVVHGHALMGK, QSLGVPPQLGNACNLDNLDVLQPTETIK, ISTINSQTLPILSQLR, PQFLVGASSILR, and VQVVNHMGQK) are 1139–2977 Da in mass and 10–28 residues in length. Such peptides are potential candidates for the future development of peptide-based anti-AHPND agents which potentially mitigate V. parahaemolyticus pathogenesis by intercepting PirAvp/PirBvp complex formation.

Proteins and peptides of housefly larvae (HFL) have potential applications in food and therapy. The fate of HFL proteins following human gastrointestinal (GI) digestion is unknown. This study adopted a computational approach to discover peptides released from HFL proteins upon GI digestion. In silico digestion of eight major HFL proteins released 783 peptides. This comprised 243 peptides exhibiting 13 types of bioactivities. Ninety-two single-function peptides exhibiting anti-dipeptidyl peptidase IV (anti-DPP-IV), anti-dipeptidyl peptidase III, anti-angiotensin converting enzyme (anti-ACE), or antioxidant activity were found. Sixty-three multi-function peptides, encompassing 32 bifunctional anti-DPP-IV and anti-ACE peptides, were found. Further screening led to five non-toxic, non-allergenic, high-GI-absorption bifunctional dipeptides: AF, GW, GY, PH, and VF. Molecular docking found the dipeptides to interact with the active site of DPP-IV through hydrophobic interactions. Only GW and VF could bind to the active site of ACE. Thus, the five dipeptides are competitive inhibitors of DPP-IV. GW and VF are potential competitive inhibitors of ACE, whereas AF, GY, and PH are non-competitive inhibitors. Overall, GI digestion could liberate numerous single- and multi-function peptides from HFL proteins. Hence, HFL proteins can be tapped for potential applications in antidiabetic and antihypertension functional food and therapy.