Which species does the virus like most: Binding modes study between SARS-CoV-2 S protein and ACE2 receptor

https://doi.org/10.1016/j.jmgm.2021.107893Get rights and content

Highlights

  • 3D structure of 17 species of ACE2 was constructed using homology modeling.

  • The interaction mode between ACE2 protein and SARS-CoV-2 S protein were simulated by MD simulation.

  • The binding free energy of S protein of SARS-CoV-2 with ACE2 was predicated using MM/PBSA.

Abstract

Background

The emergence of a novel coronavirus (SARS-CoV-2) has been spreading worldwide in 2020. Coronaviruses could mainly cause respiratory tract infections in humans and multiple system infections in many animals. The coronavirus enters the host cell through the binding of surface spike glycoprotein (S Protein) with host angiotensin-converting enzyme-Ⅱ (ACE2) protein.

Methods

ACE2 sequences of various species were aligned with human ACE2, accordingly, homology models for different species were constructed. Then, S-protein-ACE2 complexes were constructed using the generated homology models. The molecular dynamics simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) were carried out to study the dynamical behavior of the generated S-ACE2 virtual complexes. Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg) were calculated to evaluate protein stability and compactness.

Results

The binding free energies of S protein with ACE2 from Procyon lotor and Camelus dromedarius are about equal to that of humans. By comparing the free binding energies it were possible to identify potential viral hosts that could transmit the virus to human (risk of cross-species transmission). The predication showed that, besides human beings, SARS-CoV-2 may possibly infect Procyon lotor and Camelus dromedarius as well.

Keywords

SARS-CoV-2
COVID-19
Homology modeling
Molecular dynamics simulation
Binding free energy

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1

these authors contribute equally.

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