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.
Highlights
Coronavirus disease (COVID-19), a pneumonia type outbreak which was first identified in Wuhan city of China, continues to devastate lives and livelihoods across the globe
Extensive analyses have unveiled the binding of SARS-CoV-2 and ACE2 is mediated by receptor-binding domain (RBD) on the surface of S1 glycoprotein, which is a fundamental step for the virus entry (Lan et al, 2020; Shang et al, 2020; Tai et al, 2020)
Kinema produced B. licheniformis KN1G had a higher content of antiviral peptides (2.15% of total peptides), followed B. subtilis KN2B (0.76%), B. subtilis 2M (0.62%), and B. amyloliquefaciens KN2G (0.40%)
Summary
Coronavirus disease (COVID-19), a pneumonia type outbreak which was first identified in Wuhan city of China, continues to devastate lives and livelihoods across the globe. The disease has been declared as Public Health Emergency on international concern by the WHO, and till date there have been 111, 762, 965 confirmed cases and 2, 479, 678 deaths globally. The increasing prevalence of this disease has been witnessed in India, accounting for about 11, 046, 914 identified cases including 1, 56, 705 deaths and recovery of 10, 738, 501 individuals. Through its homo-trimeric spike glycoprotein (S1 and S2 subunit in each spike monomer) on the envelope, the virus enters the human cells and binds to host ACE2 cell receptors. Extensive analyses have unveiled the binding of SARS-CoV-2 and ACE2 is mediated by receptor-binding domain (RBD) on the surface of S1 glycoprotein, which is a fundamental step for the virus entry (Lan et al, 2020; Shang et al, 2020; Tai et al, 2020). Blocking the RBD or manipulating its essential residues crucial in binding hACE2 could ascertain potential therapeutics to prevent SARS-CoV-2 entry and its further infection
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