An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants.

Trina Ekawati Tallei,Rinaldi Idroes,Talha Zahid Yesiloglu,Wolfgang Sippl,Diah Kusumawaty,Rownak Jahan,Ismail Celik,Saeed Asiri,Mohammed Rahmatullah,Talha Bin Emran,Taha Alqahtani,Ali M Alqahtani,Shafi Mahmud,Fatimawali Fatimawali,Md Arif Khan,Afriza Yelnetty

doi:10.3389/fphar.2021.717757

Abstract

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

Highlights

Nature has an abundance of biological compounds that can be used as drug candidates to treat a wide range of diseases, both infectious and degenerative
The B.1.1.7 lineage is more difficult to neutralize than the parental virus, weakening the neutralization process by some members of a major class of public antibodies through light-chain interacting with the residue 501
The N501Y is located on the angiotensin-converting enzyme 2 (ACE2) interacting surface (Supasa et al, 2021)

Summary

Introduction

Nature has an abundance of biological compounds that can be used as drug candidates to treat a wide range of diseases, both infectious and degenerative. Research is focused on discovering therapeutic agents that are derived from natural ingredients, such as plant materials. Pineapple, where the fruit is frequently consumed by the community, is one of the plants with nutraceutical properties. This plant has been used as a medicinal agent for a long time, and some of its benefits have been scientifically established. The key component of pineapple fruit and roots, is one of many active compounds found in pineapple that possesses therapeutic properties. Ananain, comosain, protease inhibitors, and organically bound calcium are all present in pineapple bromelain (Gautam et al, 2010; Bala et al, 2013)

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