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SARS Coronavirus One and Two Shared Resemblance Conceals Very Different Behavioral Patterns

Published on May 15, 2020 by John Holden



The coronavirus spike protein just before binding to human cell receptor. [Credit: Moradi]

Coronavirus isn't new – it's been known to science since the 1960s. Most recently, SARS 1 coronavirus triggered a global pandemic in 2003. Except back then, about 8,000 people got infected, and around 774 died – a fraction of the current numbers due to SARS 2 that leads to COVID-19.

The two virus strains are physically very similar, with the exception of minor variations in the amino acids including some that bind to the human ACE2 receptor. So when in March the WHO declared the current outbreak a pandemic, some in the scientific community may have assumed we'd be facing a similar threat.

They couldn't have been more mistaken.

Mahmoud Moradi, University of Arkansas. [Photo by University Relations/University of Arkansas.]

As researchers worldwide are racing to defeat COVID-19, a team led by Mahmoud Moradi, a computational chemist from the University of Arkansas, may have shed new light on the differences in behavior of the two strains of the virus.

Using the Frontera and Longhorn supercomputers at the Texas Advanced Computing Center (TACC) via the COVID-19 HPC Consortium, the researchers have created enhanced 3D simulations of the molecular dynamics of coronavirus spike glycoproteins. These sugar-coated proteins make up the shell around the virus' outer probes. Mapping how they change shape to bind to host cell receptors is critical to the development of coronavirus vaccines and therapeutics.

"In the last few weeks, we have gathered a lot of data and developed the most extensive set of simulations on SARS-CoV-1 and -2 spike proteins, made possible through our access to TACC's facilities," says Moradi. "It is one of the few supercomputing facilities in the world that allows for such a quick turnaround in terms of performing such large-scale biomolecular simulations."

Simulations are especially important because to design a new drug, it's crucial to have dynamic 3D visualizations of protein structures and behavior rather than a static picture. During the simulations, Moradi and his team found that the two strains of the virus have very different dynamics – which wasn't be possible to notice just by looking at a static lab structure.

It's like two people that look alike but behave very differently, says Moradi – "in the same way, a synthesized lab structure is the equivalent of a still photo of two people. It can tell you what something looks like, but it can't tell you how it's going to behave."

Animation showing how the coronavirus spike protein changes its shape just before binding to human cell receptor.

The researchers found that the CoV-2 strain binds to human cells much tighter than its predecessor. "Our simulations show clearly just how active these proteins become," he adds.

This difference in behavior hasn't been previously noticed in any publications based on lab structures of the virus. That might be mainly because scientists attempting to synthesize the virus add different elements and make modifications to make structures stable and rigid. They also need to keep the coronavirus structures at very low temperature to ensure their stability, compromising the accuracy of these structural snapshots.

But with computational modeling, Moradi used the correct temperature and composition of the virus' environment. His team's models indicate SARS-CoV-2 spike proteins start to become active in a matter of microseconds, significantly faster than SARS-CoV-1, which favors an inactive state. It means that SARS-CoV-2 infects human cells faster and in greater amounts than SARS-CoV-1.

The discovery is just a piece of a much larger puzzle. And the faster scientists can piece such insights together, the sooner we will be able to defeat the virus and stop the pandemic.


Story Highlights

In 2003, the SARS-CoV-1 global pandemic resulted in about 8,000 total infections worldwide and less than 800 deaths – a fraction of the current number caused by SARS-CoV-2, the strain that causes COVID-19.

Because the two virus strains are physically very similar, many scientists assumed we were facing a similar threat to 2003's outbreak.

3D simulations of the molecular dynamics of coronavirus spike glycoproteins on TACC supercomputers show there are significant behavioral differences between the two strains.

The CoV-2 strain binds to human cells much tighter than its predecessor — a difference that could have major implications for understanding how we successfully treat the virus in its current form.


Contact

Faith Singer-Villalobos

Communications Manager
faith@tacc.utexas.edu | 512-232-5771

Aaron Dubrow

Science And Technology Writer
aarondubrow@tacc.utexas.edu

Jorge Salazar

Technical Writer/Editor
jorge@tacc.utexas.edu | 512-475-9411