Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2.

COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (Mpro), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were predicted using various online tools. The molecular interactions between Mpro and the peptides were studied using molecular docking and molecular dynamic simulation. The results demonstrated that peptide GSRY was predicted to have better physicochemical properties, and the value of '-C DOCKER interaction energy' between peptide GSRY and Mpro was 80.8505 kcal/mol. The interaction between the peptide GSRY and the native ligand N3 co-crystallized with Mpro had overlapped amino acids, i.e., HIS163, GlY143, GLU166, GLN189 and MET165. Molecular dynamic simulation revealed that Mpro/GSRY complexes were stable. Collectively, the peptide GSRY may be a potential candidate drug against Mpro of SARS-CoV-2.

Identification of nut protein-derived peptides against SARS-CoV-2 spike protein and main protease.

Recently, an outbreak of a novel coronavirus disease (COVID-19) has reached pandemic proportions, and there is an urgent need to develop nutritional supplements to assist with prevention, treatment, and recovery. In this study, SARS-CoV-2 inhibitory peptides were screened from nut proteins in silico, and binding affinities of the peptides to the SARS-CoV-2 main protease (Mpro) and the spike protein receptor-binding domain (RBD) were evaluated. Peptide NDQF from peanuts and peptide ASGCGDC from almonds were found to have a strong binding affinity for both targets of the coronavirus. The binding sites of the NDQF and ASGCGDC peptides are highly consistent with the Mpro inhibitor N3. In addition, NDQF and ASGCGDC exhibited an effective binding affinity for amino acid residues Tyr453 and Gln493 of the spike RBD. Molecular dynamics simulation further confirmed that the NDQF and ASGCGDC peptides could bind stably to the SARS-COV-2 Mpro and spike RBD. In summary, nut protein may be helpful as nutritional supplements for COVID-19 patients, and the screened peptides could be considered a potential lead compound for designing entry inhibitors against SARS-CoV-2.

Identification of tuna protein-derived peptides as potent SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation.

The present study aimed to identify potential SARS-CoV-2 inhibitory peptides from tuna protein by virtual screening. The molecular docking was performed to elicit the interaction mechanism between targets (Mpro and ACE2) and peptides. As a result, a potential antiviral peptide EEAGGATAAQIEM (E-M) was identified. Molecular docking analysis revealed that E-M could interact with residues Thr190, Thr25, Thr26, Ala191, Leu50, Met165, Gln189, Glu166, His164, His41, Cys145, Gly143, and Asn119 of Mpro via 11 conventional hydrogen bonds, 9 carbon hydrogen bonds, and one alkyl interaction. The formation of hydrogen bonds between peptide E-M and the residues Gly143 and Gln189 of Mpro may play important roles in inhibiting the activity of Mpro. Besides, E-M could bind with the residues His34, Phe28, Thr27, Ala36, Asp355, Glu37, Gln24, Ser19, Tyr83, and Tyr41 of ACE2. Hydrogen bonds and electrostatic interactions may play vital roles in blocking the receptor ACE2 binding with SARS-CoV-2.