To Beat Covid-19, Scientists Try to ‘See’ the Invisible Enemy

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But the CDC illustration is far from the full picture. For one thing, each virus particle is not identical. Researchers have now observed that some virus particles are spherical, while others are more egg-shaped. Their sizes vary, with diameters ranging from 80 to 160 nanometers. Lined up side by side, nearly 1,000 coronaviruses would fit across the width of an eyelash.

Courtesy of CDC

In addition, the envelope of the virus isn’t actually grey, and its spikes aren’t red—the pathogen is too small to have color. What humans perceive as color is primarily the consequence of light waves reflecting off of—or being absorbed by—the surfaces of objects. But the coronavirus is smaller than visible light itself. Its diameter is some three times narrower than the wavelength range of violet light, the visible light with the shortest wavelengths.

“It is very much an artistic interpretation,” says Alissa Eckert, the medical illustrator who made the CDC portrait with colleague Dan Higgins. “It’s purposely simplified into what communicates the best.”

Drug and vaccine design require much more scientifically precise images. Researchers are magnifying the microbe by more than 40,000 times, taking extreme close-ups to understand its structural intricacies. For example, in February, biologist Jason McLellan of the University of Texas at Austin and his team released highly-magnified 3D images of the coronavirus’s spike protein.

The team did not study the spike protein as it exists in the wild, attached to the surface of a real virus. Instead, they recreated the part of the virus’s genome, which scientists in China publicly released on January 11, that contains the instructions to make the protein. McLellan’s team inserted those genes into cultured human embryonic kidney cells, which then produced those spike proteins. They extracted those proteins and imaged them.

McLellan’s team imaged the protein spike using a method known as cryo-electron microscopy, in which they fired a thin beam of electrons at frozen, individual proteins clinging to a fine mesh. The electrons, traveling near the speed of light, bounce off the atoms of the protein onto a detector. The resulting pattern on the detector forms an image. The researchers repeat the process to create thousands of images of proteins on the mesh, all oriented in different directions. “You then use algorithms to try to recreate the object that could give all those different views,” says McLellan.

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Other researchers also use a method called X-ray crystallography to study the virus’s structure. In this method, they take multiple copies of the biological molecule in question and arrange them in neat rows to form a crystal. Then, they beam X-rays at the crystal, and can infer the virus’s structure from the areas of shadow and brightness formed by the transmitted X-rays. They use the crystalline form of the molecules because it reduces the number of X-rays they have to use—X-rays can blow the molecule into smithereens if applied at too high of a dose. (Rosalind Franklin discovered the double-helix structure of DNA using X-ray crystallography.)

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