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The Scientists Taking Atomic-Level Pictures Of The Coronavirus

This article is more than 3 years old.

The novel coronavirus, named SARS-CoV-2 and the disease it causes named coronavirus disease 2019, or COVID-19, is sweeping across the planet. It packs an outer armament of 27 specialized proteins, each one having a unique and incredibly complex 3-dimensional structure that helps the virus infect humans, replicate itself by the billions, and spread throughout the host and our society.

As represented in this image, the virus’ surface, or envelope, is studded with these proteins that are used, among other things, to attach to host cells.

Fortunately, those 27 proteins present scientists with 27 targets and 27 potential opportunities to stop the virus. 

Even before the word “coronavirus” inserted itself into the nation’s vocabulary, a national group of scientists jumped into the effort to start revealing those protein structures, structures that hold the keys to vaccines and treatments.

Scientist Garry Buchko at PNNL in Richland, Washington is part of this group. Buchko, who has a joint appointment at Washington State University’s School of Molecular Biosciences, also collaborates with scientists at the Seattle Structural Genomics Center for Infectious Disease (SSGCID) to look for any sign of the virus’ weakness that scientists can use to mess with the virus’s inner workings.

Creating atomic-level pictures of these protein structures is the first crucial step in achieving this.

Buchko and his SSGCID collaborators are looking carefully at the coronavirus proteins. Scientists get an image of many protein structures by using X-ray crystallography, which yields an extraordinary snapshot at the atomic level.

But some proteins resist this process mainly because they can’t be crystallized. That’s where Buchko comes in. [see video below for an explanation in his own words] He can tackle the toughest proteins by using nuclear magnetic resonance (NMR) spectroscopy – a cousin to magnetic resonance imaging used widely in the medical field.

“A load of 27 different proteins is fairly large for a virus,” says Buchko. “We need to understand the role that each one plays in allowing the virus to hijack human host cells to replicate.”

Buchko does not work directly with the entire coronavirus. Rather, he and his Seattle colleagues use snippets of genetic code to study one protein at a time by growing the individual proteins in bacteria. Unlike the virus itself, the individual proteins are harmless.

From there, other scientists at SSGCID solve the bulk of the protein structures using X-rays, while Buchko turns his focus to the subset that resists crystallography by using NMR. NMR has an added advantage in that it allows scientists to watch a protein in action in a way other methods do not.

Ultimately, after weeks of data collection, Buchko is left with thousands of pieces of data. He feeds that into a computer program to calculate the position of every single atom, resulting in a complete 3D reconstruction of the protein (see figure below). That’s crucial information for scientists around the globe who are working on ways to stop the virus, supplying them with a how-to guide to identify viral vulnerabilities.

This isn’t the first time this team has attacked a deadly microbe. In the 13 years since its creation, SSGCID and PNNL scientists have solved the structures of almost 1,300 proteins from over 70 organisms that cause human death and disease.

The group has brought discovery to bear on diseases like tuberculosis, the plague, Ebola and the flu. The structures help scientists develop better treatments or vaccines against a host of nasty agents that can cause ills ranging from fatigue and food poisoning to difficulty breathing, and death.

The data from all these microbial structures are immediately shared with the scientific community through a public database called the Protein Data Bank, to be used by other laboratories in academia, research institutes, and pharmaceutical companies around the world that are working on human pathogens. Sharing its findings so that scientists worldwide can make further discoveries is at the heart of SSGCID's mission.

“In our current work, our hope is that others can use our findings as blueprints for drug design. Perhaps they will be able to pluck out a specific site on the protein for targeting that will weaken the virus’s virulence,” saya Buchko.

Indeed, it is not hyperbole to say this is life-saving research.

This type of research is conducted on all microbes and molecular complexes, not just pathogens. Shown above is the light-harvesting protein supercomplex from the photosynthetic cyanobacteria, the most ancient of all photosynthetic organisms, and one that played a crucial role in developing our present oxygenated atmosphere. These images show individual protein molecules, so the whole image isn’t much bigger than a billionth of an inch.

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