Scrutiny of the mechanism of β-amyloid protein captures HSV-2 to protect the brain infection

Qiuxian Zhang,Hecheng Wang,M.M.H Mostafa,S Manickam

doi:10.1051/e3sconf/202126102069

Qiuxian Zhang, Hecheng Wang + Show 2 more

Open Access

https://doi.org/10.1051/e3sconf/202126102069

Copy DOI

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. β-amyloid protein (Aβ) is the key protein which involved in AD. But the physiological function of Aβ is needed to be investigated. Many experimental studies have shown that Aβ could bind to glycoproteins D (gD) on the surface of the herpes virus. However the mechanism is still unclear. In the present study, we elucidate the molecular mechanism of the interaction between Aβ and gD of herpes simplex virus type 2 (HSV-2) by molecular docking and molecular dynamics simulation. Molecular dynamics simulations displayed that Aβ could stably bind to the HSV-2 gD owing to the presence of several interactions. Analysis binding free energy by molecular mechanics Poisson–Boltzmann surface area (MM–PBSA) method revealed that hot residues including Glu3, Glu11, Glu22 and Ala42 of Aβ1-42 were involved in binding with HSV-2 gD. Thus, the HSV-2 gD can be entrapped by Aβ which will be utilized for prevent and therapy of AD in future.

Highlights

Alzheimer’s disease (AD) is a chronic neurodegenerative disease [1]. β-amyloid protein (Aβ) deposition in the brain is considered as the main neuropathology characteristics of AD
It was found that viral infections may be a risk factor for neurodegenerative diseases, and many studies have revealed the link between herpes simplex virus type 2 (HSV-2) and AD [4, 5]
The best docked complex was solvated in a cubic box with simple point charge (SPC) water model [7]

Summary

Introduction

Alzheimer’s disease (AD) is a chronic neurodegenerative disease [1]. β-amyloid protein (Aβ) deposition in the brain is considered as the main neuropathology characteristics of AD. Β-amyloid protein (Aβ) deposition in the brain is considered as the main neuropathology characteristics of AD. The deposition of Aβ may be considered as a protective innate immune response to infection [2, 3]. The aggregation of misfolded of Aβ may be caused by excessive activation of the immune response in the brain. It was found that viral infections may be a risk factor for neurodegenerative diseases, and many studies have revealed the link between herpes simplex virus type 2 (HSV-2) and AD [4, 5]. HSV-2 is a neurotropic virus, which can establish a latent infection in trigeminal ganglia at infected individuals [5]. The present work illustrates the innate immune roles of Aβ at the molecularlevel

Protein-protein docking

Evaluation of binding free energy

The prediction of binding mode and key interactions of HSV-2 gD Aβ1-42 compex

Binding mode analysis

Analysis the molecular interaction between HSV-1 and Aβ by MM–PBSA

Conclusion