In silico evaluation of marine fish proteins as nutritional supplements for COVID-19 patients.

To date, no specific drug has been discovered for the treatment of COVID-19 and hence, people are in a state of anxiety. Thus, there is an urgent need to search for various possible strategies including nutritional supplementation. In this study, we have tried to provide a reference for protein supplementation. Specifically, 20 marine fish proteins were subjected to in silico hydrolysis by gastrointestinal enzymes, and a large number of active peptides were generated. Then, the binding abilities of these peptides to SARS-CoV-2 main protease and monoamine oxidase A were assessed. The results showed that NADH dehydrogenase could be a good protein source in generating potent binders to the two enzymes, followed by cytochrome b. In addition, some high-affinity oligopeptides (VIQY, ICIY, PISQF, VISAW, AIPAW, and PVSQF) were identified as dual binders to the two enzymes. In summary, the supplementation of some fish proteins can be helpful for COVID-19 patients; the identified oligopeptides can be used as the lead compounds to design potential inhibitors against COVID-19 and anxiety.

Isolation and characterization of ACE-I inhibitory peptides from ribbonfish for a potential inhibitor of the main protease of SARS-CoV-2: An in silico analysis.

Recently, multifunctional fish peptides (FWPs) have gained a lot of attention because of their different biological activities. In the present study, three angiotensin-I converting enzyme (ACE-I) inhibitory peptides [Ala-Pro-Asp-Gly (APDG), Pro-Thr-Arg (PTR), and Ala-Asp (AD)] were isolated and characterized from ribbonfish protein hydrolysate (RFPH) and described their mechanism of action on ACE activity. As per the results, peptide PTR showed ≈ 2 and 2.5-fold higher enzyme inhibitory activity (IC50 = 0.643 ± 0.0011 µM) than APDG (IC50 = 1.061 ± 0.0127 µM) and AD (IC50 = 2.046 ± 0.0130 µM). Based on experimental evidence, peptides were used for in silico analysis to check the inhibitory activity of the main protease (PDB: 7BQY) of SARS-CoV-2. The results of the study reveal that PTR (-46.16 kcal/mol) showed higher binding affinity than APDG (-36.80 kcal/mol) and AD (-30.24 kcal/mol) compared with remdesivir (-30.64 kcal/mol). Additionally, physicochemical characteristics of all the isolated peptides exhibited appropriate pharmacological properties and were found to be nontoxic. Besides, 20 ns molecular dynamic simulation study confirms the rigid nature, fewer confirmation variations, and binding stiffness of the peptide PTR with the main protease of SARS-CoV-2. Therefore, the present study strongly suggested that PTR is the perfect substrate for inhibiting the main protease of SARS-CoV-2 through the in silico study, and this potential drug candidate may promote the researcher for future wet lab experiments.

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.