The COVID-19 virus holds some mysteries. Scientists remain in the dark on aspects of how it fuses and enters the host cell; how it assembles itself; and how it buds off the host cell.

A new multiscale coarse-grained model of the complete SARS-CoV-2 virion, its core genetic material and virion shell, has been developed for the first time using supercomputers. The model offers scientists the potential for new ways to exploit the virus’s vulnerabilities.

“We wanted to understand how SARS-CoV-2 works holistically as a whole particle,” said Gregory Voth, the Haig P. Papazian Distinguished Service Professor at the University of Chicago. Voth is the corresponding author of the study that developed the first whole virus model, published November 2020 in the Biophysical Journal.

“We developed a bottom-up coarse-grained model,” said Voth, “where we took information from atomistic-level molecular dynamics simulations and from experiments.” He explained that a coarse-grained model resolves only groups of atoms, versus all-atom simulations, where every single atomic interaction is resolved. “If you do that well, which is always a challenge, you maintain the physics in the model.”

The early results of the study show how the spike proteins on the surface of the virus move cooperatively.

“They don’t move independently like a bunch of random, uncorrelated motions,” Voth said. “They work together.”

This cooperative motion of the spike proteins is informative of how the coronavirus explores and detects the ACE2 receptors of a potential host cell.

“The paper we published shows the beginnings of how the modes of motion in the spike proteins are correlated,” Voth said. He added that the spikes are coupled to each other. When one protein moves another one also moves in response.

“The ultimate goal of the model would be, as a first step, to study the initial virion attractions and interactions with ACE2 receptors on cells and to understand the origins of that attraction and how those proteins work together to go on to the virus fusion process,” Voth said.

Image Credit:   Gregory Voth, University of Chicago

Post by Amanda Scott, NA CEO.  Follow her on twitter @tantriclens

Thanks to Heinz V. Hoenen.  Follow him on twitter: @HeinzVHoenen