Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause respiratory distress and even death in severe cases. The disease manifested is called COVID-19 (coronavirus disease 2019). To date, no specific antiviral drug is available to treat the highly virulent SARS-CoV-2 infections in humans.
A recent study in the journal Food Chemistry draws attention to the need for finding nutritional supplements with potential SARS-CoV-2 inhibition effects in the wake of the COVID-19 pandemic.
Performing molecular docking, the study’s researchers identified an antiviral peptide EEAGGATAAQIEM (E-M) as a potential SARS-CoV-2 inhibitor. They found that the peptide interacts with the residues Thr190, Thr25, Thr26, Ala191, Leu50, Met165, Gln189, Glu166, His164, His41, Cys145, Gly143, and Asn119 of the Main Protease of SARS-CoV-2 (Mpro) via 11 conventional hydrogen bonds, 9 carbon-hydrogen bonds, and one alkyl interaction.
Additionally, they found that E-M also binds ACE2 – the receptor which mediates viral entry – with the residues His34, Phe28, Thr27, Ala36, Asp355, Glu37, Gln24, Ser19, Tyr83, and Tyr41. This study is indicative that hydrogen bonds and electrostatic interactions may play vital roles in blocking the receptor ACE2 binding with SARS-CoV-2.
The main protease (Mpro, also called 3CLpro) in the SARS-CoV-2 virus is a necessary therapeutic target. Together with papain-like proteases, it plays a vital role in RNA translation and recognizes specific cleavage sites. Inhibiting this enzyme activity would help block viral replication. Also, because no human protease with similar cleavage specificity is known, such inhibitors are unlikely to be toxic to humans.
ACE2 (angiotensin-converting enzyme 2) is the human host receptor to SARS-CoV-2 spike (S) protein, initiating the viral entry into human cells. The researchers thus construed that blocking the interaction between the S protein of SARS-CoV-2 and receptor-binding domain (RBD) of cellular receptors ACE2 can prevent virus entry. Therefore, ACE2 is also an attractive target for the treatment of SARS-CoV-2.
As a nutritional supplement, this protein may be a helpful approach to improve immunity against SARS-CoV-2. Many previous studies have reported peptides as potential therapeutic agents (such as anti-HIV C-peptide (SJ-2176) and enfuvirtide). This is chiefly because of their selectivity, specificity, low levels of side effects, and predictable metabolism.
The researchers evaluated the binding abilities of peptides to Mpro and ACE2. They expected that the peptides with high affinity to the two enzymes could be expected to have some potential inhibition on SARS-CoV-2.
However, isolating, purifying and identifying bioactive peptides from protein hydrolysates are highly extensive and time-consuming processes. It can be simplified and accelerated by multistep virtual screening method and in silico gastrointestinal (GI) digestion.
For which the researchers identified tuna-derived peptides for their study, that can be used as nutritional supplementation and also have potential inhibition of SARS-CoV-2 activity. Tuna, high content of nutrition ingredients food, has been found to inhibit the ACE2 receptor.
The goal of this study was to identify novel peptides for COVID-19 patients from tuna protein as nutritional supplementation, using a combination strategy of in silico hydrolysis and molecular docking. The tests were performed to discover novel inhibitory peptides against Mpro and the host receptor ACE2.
The researchers explain in the paper that molecular docking involves docking peptides with the active center of targets in a Discovery Studio (DS) software. Here, they used DS 2017 R2 software. This generates the CDOCKER energy in the process. This CDOCKER energy predicts the stability of the peptide-target interaction.
In this study, they evaluated the CDOCKER-energy value of the peptide E-M with ACE2 as 144 kcal/mol. This is indicative that the active site of ACE docked with SARS-CoV-2 spike was strongly occupied by peptide E-M, which could affect/inhibit the SARS-CoV-2 activity.
They also performed molecular dynamic simulations (MD) to determine the binding affinity of the peptide with the main protease, Mpro, and ACE2 of SARS-CoV-2 at room temperature.
From this study, the researchers found that the peptide E-M from the skeletal myosin of tuna is a potential ‘SARS-CoV-2 inhibitory’ candidate. Using the molecular docking simulation, they demonstrated the amino acids (Gly143 and Gln189) that played important roles in the interactions of peptides E-M and Mpro.
Significantly, they found that the peptide E-M could block SARS-CoV-2 attachment to host cells by connecting with virus receptor ACE2 via hydrogen bonds and electrostatic interactions.
They recommended the safe use of peptide E-M because of their dietary source potential as a good nutritional supplementation for COVID-19 patients. However, they call for ex vivo and in vivo experiments that can verify the applicability of their findings from this study.