A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein

Abstract

The COVID-19 pandemic caused by novel SARS-CoV-2 has resulted in an unprecedented loss of lives and economy around the world. In this study, search for potential inhibitors against two of the best characterized SARS-CoV-2 drug targets: S1 glycoprotein receptor-binding domain (RBD) and main protease (3CL^Pro), was carried out using the soy cheese peptides. A total of 1,420 peptides identified from the cheese peptidome produced using Lactobacillus delbrueckii WS4 were screened for antiviral activity by employing the web tools, AVPpred, and meta-iAVP. Molecular docking studies of the selected peptides revealed one potential peptide "KFVPKQPNMIL" that demonstrated strong affinity toward significant amino acid residues responsible for the host cell entry (RBD) and multiplication (3CL^pro) of SARS-CoV-2. The peptide was also assessed for its ability to interact with the critical residues of S1 RBD and 3CL^pro of other β-coronaviruses. High binding affinity was observed toward critical amino acids of both the targeted proteins in SARS-CoV, MERS-CoV, and HCoV-HKU1. The binding energy of KFVPKQPNMIL against RBD and 3CL^pro of the four viruses ranged from -8.45 to -26.8 kcal/mol and -15.22 to -22.85 kcal/mol, respectively. The findings conclude that cheese, produced by using Lb. delbrueckii WS4, could be explored as a prophylactic food for SARS-CoV-2 and related viruses. In addition, the multi-target inhibitor peptide, which effectively inhibited both the viral proteins, could further be used as a terminus a quo for the in vitro and in vivo function against SARS-CoV-2.

Keywords: Lactobacillus delbrueckii WS4; S1 glycoprotein; main protease; peptides; soy cheese.

Figure 1

Distribution of antiviral peptides among their proteins of origin in soy cheese produced using Lactobacillus delbrueckii WS4.

Figure 2

Receptor-ligand interactions between SARS-CoV-2 RBD and KFVPKQPNMIL. (A) Illustration showing molecular docking of KFVPKQPNMIL with RBD of S1 glycoprotein. RBD surface is represented by H-bond donor and acceptor atoms. (B) 3D interpretation representing structural interaction between peptidyl and RBM residues. (C) 2D diagram of peptide-RBD interactions including hydrogen bonds, Pi-Sulfur, Alkyl, and unfavorable interactions.

Figure 3

Receptor-ligand interactions between SARS-CoV-2 3CL^pro and KFVPKQPNMIL. (A) Illustration showing molecular docking of KFVPKQPNMIL with active site of 3CL^pro. 3CL^pro surface is represented by H-bond donor and acceptor atoms. (B) 3D interpretation representing structural interaction between peptidyl and 3CL^pro residues. (C) 2D diagram of peptide-3CL^pro interactions including hydrogen bonds, Pi-Sulfur, Pi-Sigma, and Alkyl bonds.

Figure 4

KFVPKQPNMIL interaction with RBD of SARS-CoV (A), MERS-CoV (B), and HCoV-HKU1 (C). 3D illustration of complex between KFVPKQPNMIL-SARS-CoV RBD (A1), KFVPKQPNMIL-MERS-CoV RBD (B1), and KFVPKQPNMIL-HCoV-HKU1 RBD (C1). RBD surface is represented by H-bond donor and acceptor atoms. 2D representation of different bonds formed during KFVPKQPNMIL interaction with RBD of SARS-CoV (A2), MERS-CoV (B2), and HCoV-HKU1 (C2).

Figure 5

KFVPKQPNMIL interaction with 3CL^pro of SARS-CoV (A), MERS-CoV (B), and HCoV-HKU1 (C). 3D illustration of complex between KFVPKQPNMIL-SARS-CoV 3CL^pro (A1), KFVPKQPNMIL-MERS-CoV 3CL^pro (B1), and KFVPKQPNMIL-HCoV-HKU1 3CL^pro (C1). 3CL^pro surface is represented by H-bond donor and acceptor atoms. 2D representation of different bonds formed during KFVPKQPNMIL interaction with 3CL^pro of SARS-CoV (A2), MERS-CoV (B2), and HCoV-HKU1 (C2).