Screening and Molecular Modeling Evaluation of Food Peptides to Inhibit Key Targets of COVID-19 Virus

Abstract

Peptide drugs, especially food-derived peptides, have a variety of functional activities including antiviral and may also have a therapeutic effect on COVID-19. In this study, comparing with the reported drugs, 79 peptides were found to bind to the key targets of COVID-19 virus with higher non-covalent interaction, while among them, six peptides showed high non-covalent interactions with the three targets, which may inhibit the COVID-19 virus. In the simulation, peptides of nine to 10 amino acids with a hydrophilic amino acid and acidic amino acid in the middle and aromatic amino acids on the side showed higher binding to angiotensin-converting enzyme 2 (ACE2). Peptides of five to six amino acids with a basic amnio acid in the head, acidic amnio acid in the neck, hydrophobicity group in the middle, and basic amino acids in the tail showed higher binding to COVID-19 virus main protease (Mpro), while those with basic amino acids and acidic amino acids in the two sides and aromatic amino acids in the middle might have stronger interaction with COVID-19 virus RNA-dependent RNA polymerase (RdRp).

Predicting global diet-disease relationships at the atomic level: a COVID-19 case study

“…Although some of the studies in this overview included molecular dynamics as a post-docking assessment, many lack additional data processing steps. The short production times of molecular dynamic simulations used in some studies also risk missing important changes in binding stability [ 43 , 47 , 58 ], changes of which occur over timescales of 100–200 ns [ 19 , 22 • ]. Specific workflows may also be required depending on the analytes evaluated.…”

“…Wahedi et al [ 46 ] evaluated stilbenes, which are associated with anti-tumor, anti-inflammatory, and other biological activities, with the aim of repurposing them as agents against COVID-19 and found that resveratrol may have potent activity inhibiting the host-virus interactions mediated by SARS-CoV-2 spike protein. Food-derived peptides with purported anti-hypertensive activity were predicted to interact with various targets of SARS-CoV-2 and demonstrated potential as lead compounds for COVID-19 treatment [ 47 ]. Nisin, a well-established and common food preservative with known antimicrobial activity, was reported for the first time to potentially possess antiviral activity via interactions with human angiotensin-converting enzyme 2, a protein involved in coronavirus-host recognition [ 48 ].…”

Bioactive peptides of plant origin: distribution, functionality, and evidence of benefits in food and health

“…The hydrophobicity of macrocyclic peptides is related to the anti-HIV activity; however, the mechanism of action is still unclear. 39,40 In a recent study, Shi et al (2021) successfully demonstrated that 79 peptides derived from natural food resources, including plant, animal, marine, and mushroom, can bind to key targets of the COVID-19 virus and may thus exert antiviral activity. 41 Among them, VSGAGRY from bitter melon seed, VMDKPQG from soybean, KDYRL from mung bean, NNNPFKF…”

SARS‐CoV‐2 main protease inhibitors: What is moving in the field of peptides and peptidomimetics?

“…In another appealing work, Shi and coworkers reported the identification of candidate foodderived peptides with ability to bind to three of the most important targetable SARS-CoV-2 proteins, namely angiotensin-converting enzyme type 2 (ACE2), key for viral entry, Mpro, and reversed transcriptase (RdRp) [24] . As for Mpro, the computational studies detected about 150 peptides able to occupy the protease binding site, and the interaction of the 30 highscored compounds were analyzed in detail.…”