In Silico Analysis of Inhibiting Papain-like Protease from SARS-CoV-2 by Using Plant-Derived Peptides

SARS-CoV-2 is a corona virus that has been the cause for one of the deadliest pandemics of history, started since 2019. Suppressing the activity of the critical enzymes in the SARS-CoV-2 could potentially inhibit a vital step in viral life cycle. Papain-like protease (PLpro) could be regarded as a critical enzyme in viral replication of SARS-CoV-2. In this research, it was aimed to suppress the activity of PLpro enzyme by using potential plant-derived protease inhibitor peptides. For this purpose, 11 plant derived peptides that could potentially inhibit protease activity were selected from literature. The structures of the PLpro and the peptide ligands were acquired from PDB (protein data bank) and after structural optimization, were docked by using HADDOCK 2.4 program. Analyzing the results indicated that VcTI from Veronica hederifolia provides effective molecular interactions at both liable Zn site and classic active site of PLpro, making it a potential inhibitory ligand for this enzyme that could be used for halting the replication of SARS-CoV-2. Molecular dynamic assay confirmed that the selected receptor and ligand complex was stable. Future in vitro and in vivo investigations are required to verify the efficiency of this compound as a potential therapeutic against SARS-CoV-2 infection.

Automated summary

The study aimed to suppress the activity of a critical enzyme in SARS-CoV-2 using plant-derived protease inhibitor peptides, with VcTI identified as a potentially effective inhibitory ligand. Molecular dynamic assay confirmed the stability of the selected receptor and ligand complex, further in vitro and in vivo investigations are needed to verify the therapeutic efficiency of this compound against SARS-CoV-2 infection.