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.
【저자키워드】 SARS-CoV-2, Mutation, variants, Receptor-binding domain, Bromelain, 【초록키워드】 COVID-19, Treatment, mutations, variant, molecular docking, in vitro, antiviral activity, virus, binding affinity, binding site, hACE2, Molecular dynamics simulation, Novel coronavirus, Spread, Protein, stability, SARS-CoV-2 variants, RBD, Research, molecular, in vivo, inhibitor, RBD protein, binding, RMSD, Interaction, Potential treatment, antiviral property, viral spike protein, potential mechanism, approaches, enzyme, complex, inhibitory effect, human Angiotensin-converting enzyme, treat, new virus, while, RBD proteins, Prevent, new SARS-CoV-2, bind, shown, resulting, indicated, remained, required, approved, exhibited, changes in, the receptor-binding domain, complexes, increases in, destabilized, RBD variant, the SARS-CoV-2, 【제목키워드】 Dynamics, Simulation,