A Multifunctional Peptide From Bacillus Fermented Soybean for Effective Inhibition of SARS-CoV-2 S1 Receptor Binding Domain and Modulation of Toll Like Receptor 4: A Molecular Docking Study

Abstract

Fermented soybean products are traditionally consumed and popular in many Asian countries and the northeastern part of India. To search for potential agents for the interruption of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike glycoprotein 1 (S1) and human angiotensin-converting enzyme 2 (ACE2) receptor interactions, the in silico antiviral prospective of peptides identified from the proteome of kinema was investigated. Soybean was fermented using Bacillus licheniformis KN1G, Bacillus amyloliquefaciens KN2G and two different strains of Bacillus subtilis (KN2B and KN2M). The peptides were screened in silico for possible antiviral activity using two different web servers (AVPpred and meta-iAVP), and binding interactions of selected 44 peptides were further explored against the receptor-binding domain (RBD) of the S1 protein (PDB ID: 6M0J) by molecular docking using ZDOCK. The results showed that a peptide ALPEEVIQHTFNLKSQ (P13) belonging to B. licheniformis KN1G fermented kinema was able to make contacts with the binding motif of RBD by blocking specific residues designated as critical (GLN493, ASN501) in the binding of human angiotensin-converting enzyme 2 (ACE2) cell receptor. The selected peptide was also observed to have a significant affinity towards human toll like receptor 4 (TLR4)/Myeloid Differentiation factor 2 (MD2) (PDB ID: 3FXI) complex known for its essential role in cytokine storm. The energy properties of the docked complexes were analyzed through the Generalized Born model and Solvent Accessibility method (MM/GBSA) using HawkDock server. The results showed peptidyl amino acids GLU5, GLN8, PHE11, and LEU13 contributed most to P13-RBD binding. Similarly, ARG90, PHE121, LEU61, PHE126, and ILE94 were appeared to be significant in P13-TLR4/MD2 complex. The findings of the study suggest that the peptides from fermented soy prepared using B. licheniformis KN1G have better potential to be used as antiviral agents. The specific peptide ALPEEVIQHTFNLKSQ could be synthesized and used in combination with experimental studies to validate its effect on SARS-CoV-2-hACE2 interaction and modulation of TLR4 activity. Subsequently, the protein hydrolysate comprising these peptides could be used as prophylaxis against viral diseases, including COVID-19.

Beneficial Effects of Soybean-Derived Bioactive Peptides

“…The P13human TLR4/myeloid differentiation factor (MDF2) complex is known for its critical role in the cytokine storm based on in silico analysis. These results suggest that ALPEE-VIQHTFNLKSQ has greater potential to be applied as an antiviral agent and used as a prophylaxis agent against viral diseases, including coronavirus disease 2019 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Table 1) [108]. As the production of various antiviral peptides is dependent on the culture conditions of species as well as the strain, further studies of selected peptides using molecular docking systems are needed to demonstrate that the peptide interacts with the active residues of SARS-CoV-2 spike glycoprotein (S1) receptor-binding domain and the human TLR4/MDF2 complex.…”

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

“…Molecular docking mechanism confirmed that the purified peptide PTR is an excellent inhibitor for the main protease of SARS-CoV2. Similarly, Padhi et al 29 reported that fermented soybean peptides showed perfect interaction with the main protease of SARS-CoV-2. Another study reported by Wong peptides, which contain bulky side group amino acid-like arginine, proline, tryptophan, tyrosine lysine, showed higher inhibitory activity, 15 which could be the reason PTR showed the higher main protease inhibitory activity.…”

Potential of edible insects as source of functional foods: biotechnological approaches for improving functionality

“…Bioactive peptides (BP) are those peptides having a biological function or a specific protein fragments that have a positive impact on body functions or conditions and may influence health [58,60]. BP plays a major role in human health by improving the digestive, endocrine, cardiovascular, immune, and nervous systems [11,61,62]. Edible insects have peptides which are naturally present as well as those produced on enzymatic hydrolysis of insect protein.…”