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

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10989-021-10331-8.

Molecular dynamics-driven exploration of peptides targeting SARS-CoV-2, with special attention on ACE2, S protein, Mpro, and PLpro: A review

“…Some of the studies discussed in this review may contribute to the repurposing of drugs or current antiviral compounds (Chowdhury et al, 2020;Pant et al, 2020). Other reports may facilitate the discovery of novel anti-SARS-CoV-2 agents from food and other bioresources (Yu et al, 2021;Yathisha et al, 2022;Moradi et al, 2022), thereby adding value to such biomaterials. Potential SARS-CoV-2 inhibitory peptides have also been identified from many other novel bioresources, such as edible insects (Wong et al, 2020;Ong et al, 2021).…”

“…Moradi and co-workers screened 11 plant-derived peptides from the literature that could potentially inhibit PL pro activity (Moradi et al, 2022). They found that the peptide VcTI from Veronica hederifolia provided effective molecular interactions at both the liable zinc site and the classic active site of PL pro .…”

“…They found that the peptide VcTI from Veronica hederifolia provided effective molecular interactions at both the liable zinc site and the classic active site of PL pro . Eighteen residues of PL pro and 16 residues of VcTI were involved in the interactions, which were stable throughout the 20 ns of MD simulation (Moradi et al, 2022). The MD simulation of the VcTI-PL pro complex was performed using the OPLS force field with an SPC216 water model in the cubic box (Moradi et al, 2022), a relatively generic set-up for GROMACS system simulation (Lee et al, 2016).…”

“…Eighteen residues of PL pro and 16 residues of VcTI were involved in the interactions, which were stable throughout the 20 ns of MD simulation (Moradi et al, 2022). The MD simulation of the VcTI-PL pro complex was performed using the OPLS force field with an SPC216 water model in the cubic box (Moradi et al, 2022), a relatively generic set-up for GROMACS system simulation (Lee et al, 2016). Using the same force field coupled to TIP3P water models in MD analysis, Sasidharan et al (2021) demonstrated the affinity of p28, an azurinderived peptide, to PL pro based on its binding to the finger domain of the protease that houses the catalytic zinc ion.…”

Peptide-Based Strategies Against SARS-CoV-2 Attack: An Updated In Silico Perspective

“…Finally suppressing the activity of the PLpro enzyme by using potential plant-derived protease inhibitor peptides has also been considered. (Moradi et al, 2022) have tested 11 plant-derived peptides selected from the literature that could potentially inhibit protease activity. Docking experiments suggest that VcTI from Veronica hederifolia provides effective molecular interactions at both the liable Zn site and the classic active site of PLpro.…”