Molecular dynamics analysis of N-acetyl-D-glucosamine against specific SARS-CoV-2's pathogenicity factors


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Baysal Ö., Ghafoor N. A. , Silme R. S.

Other, pp.1-18, 2021

  • Publication Type: Other Publication / Other
  • Publication Date: 2021
  • Page Numbers: pp.1-18

Abstract

Background: The causative agent of virus disease outbreak in the world identified as SARS-CoV-2 leads to a severe respiratory illness similar to that of SARS and MERS. The pathogen outbreak was declared as a pandemic and by the time of this article, it has claimed 2.19 million lives. Computational biology research has provided a lot of insight into many of the structural and functional proteins of the virus and the efforts continue.

Methods: We performed molecular docking of several SARS-CoV-2 proteins that are responsible for its pathogenicity against N-acetyl-D-glucosamine via AutoDock Vina and further analyzed the docked poses with molecular dynamics, we also performed a similar experiment for both SARS-CoV-2 and anti-Staphylococcus aureus neutralizing antibodies to establish the potential N-acetyl-D-glucosamine hold in inducing the immune system against the virus.

Results: Our new molecular docking and molecular dynamic analysis results have confirmed that SARS-CoV-2 spike receptor-binding domain (PDB: 6M0J), crystal structure of RNA-binding domain of nucleocapsid phosphoprotein from SARS-CoV-2 monoclinic crystal form (PDB: 6WKP), electron microscopy structure of refusion SARS-CoV-2 S ectodomain trimer covalently stabilized in the closed conformation (PDB: 6X79), and X-ray diffraction structure of SARS-CoV-2 main protease 3clpro at room temperature (damage-free XFEL monoclinic, PDB: 7JVZ), and N-acetyl-D-glucosamine could bind on these proteins that play an important role in SARS-CoV-2’s infection. Moreover, our molecular docking analysis data support a strong protein-ligand interaction of N-acetyl-D-glucosamine. These results were confirmed with molecular dynamics studies and the conformational modeling could be used to predict the possible protein-ligand interactions. Additionally, docking analysis against the D614G mutant of the virus have shown that N-acetyl-D-glucosamine affinity was not affected by mutations in the virus’ receptor binding domain. Furthermore, our analysis on the affinity of D-GlcNAc towards human antibodies has shown that it could potentially bind to both SARS-CoV-2 proteins and antibodies hence further induce the immune system against the viral infection.

Conclusion: Based on our predictive modelling work, N-acetyl-D-glucosamine holds the potential to inhibit several SARS-CoV-2 proteins as well as induce an immune response against the virus in host system.