Coupling of SARS-CoV-2 to Aβ Amyloid Fibrils

Abstract

The COVID-19 infection has been more problematic for individuals with certain health predispositions. Coronaviruses could also interfere with neural diseases if the viruses succeed in entering the brain. Therefore, it might be of principal interest to examine a possible coupling of coronaviruses and amyloid fibrils. Here, molecular dynamics simulations were used to investigate direct coupling of SARS-CoV-2 and Aβ fibrils, which play a central role in neural diseases. The simulations revealed several stable binding configurations and their dynamics of Aβ42 fibrils attached to spike proteins of the Omicron and Alpha variants of SARS-CoV-2.

Figure 1

MD simulations of (A) nonpolar and (B) acidic sides (residues) of the Aβ42 (12-mer) fibril coupled to RBD in the spike of SARS-CoV-2 (Omicron). In a more detailed analysis, (A,B) correspond to configurations in Figure 4B,D, respectively.

Figure 2

Details of coupling between the nonpolar side of the Aβ fibril and (A) Omicron and (B) Alpha RBDs. (C) Charged side of the Aβ fibril coupled with the Omicron RBD. (D) Average coupling energies and MM/GBSA free energies calculated for the above cases. The direct coupling energies are split into Coulombic and vdW contributions. Here, (A,B,C) correspond to the configurations in Figure 4B (Omicron), 4B (Alpha), and 4D (Omicron), respectively.

Figure 3

Distances traveled in 200 ns by fibrils with (A) nonpolar and (B) acidic orientations coupled to the Alpha and Omicron RBDs. (C,D,) Binding energies calculated for these cases. The acidic orientation of the fibril departs from the Alpha RBD. (E) Time-dependent MSD calculated for the three stable cases from Figure 2A,B,C. (F) Time-dependent diffusion constants calculated for these three cases.

Figure 4

Possible stable configurations of the Aβ42 fibril on RBDs. (A) Side and top views of the RBD (Omicron) with visualized blue and red regions where the fibril (dashed) binds. The two ends of the fibril are labeled 1 and 2. (B–E) Configurations of the fibril in the two nesting areas, where the 1 end of the fibril is at the top and the views from this end along the fibril are shown. (F–I) Same when the 2 end of the fibril is at the top. The fibril-RBD binding energies in these configurations are also provided. In brackets, we report the standard deviation in kcal/mol. Figures S1–4 show contributions to these coupling energies by residues.