If You Squeeze the Coronavirus, Does It Shatter?

Scientists are exploring the physics of viruses, to understand how these pathogens assemble themselves — and might be rent apart.

A microscopic video of an RNA virus self-assembling. The dark spots are individual viruses, and they grow darker as more and more proteins attach to the RNA strand. Video by Rees F. Garmann, Aaron M. Goldfain, Vinothan N. Manoharan, PNAS 2019Credit…

Katherine J. Wu

By Katherine J. Wu

Jan. 26, 2021

Of all the pandemic questions bedeviling scientists, the one that Juan Perilla is asking might be among the strangest: If a shrunk-down hand were to squeeze the coronavirus, would it squish, or would it shatter?

Viruses like H.I.V. tend to be on the softer side, smooshing down like a foam ball, whereas the ones that cause influenza are more brittle, prone to cracking like an egg, said Dr. Perilla, a biophysical chemist at the University of Delaware in Newark. Coronaviruses, he suspects, are somewhere in the middle, a sort of tactile Goldilocks in the world of infectious disease.

“It’s something you never consider when you talk about viruses,” Dr. Perilla said. But it’s part and parcel, he added, of “trying to understand how a virion is strung together.”

Like many other microbes, viruses are known best as malady-toting motes of misfortune — obvious grist for biologists keen to understand the inner workings of infection. But in recent years, physicists too have joined the field, eager to decipher how viruses cobble themselves together and move from place to place despite lacking most of the machinery that enables cells to replicate and run.

Some physicists, like Dr. Perilla, are teasing apart the mechanical properties of virus particles, while others monitor the forces that bring the bits and pieces of viruses together or tear them apart. Some are even enlisting physics to design the next generation of Covid-19 treatments, whether by disrupting the forces that assemble viruses inside human cells or by creating a suite of self-replicating vaccines.

“Once you understand how something works, you can understand how to sabotage it,” said Jodi Hadden-Perilla, a biophysical chemist at the University of Delaware. (Dr. Perilla and Dr. Hadden-Perilla, a married couple, are professional collaborators.)

Physics and virology are now so academically intertwined that their union has acquired a formal name: virus physics (or, to some, physical virology). And the data its pioneers produce can have consequences far beyond the microbial world.

“At the end of the day,” said LaNell Williams, a virologist and physicist at Harvard University, “we’re trying to figure out what physics viruses already know.”
Simply complex
Video
Cinemagraph
A simulation showing one possible step of the coronavirus assembly process. After the virus’s genome is condensed (the sphere), it “buds” from a membrane-bound compartment, stealing a fatty coat (the web-like matter that forms a bubble around the sphere). Part of this process involves forcing the host membrane to curve around the virus’s genome. Video by Roya Zandi, University of CaliforniaCredit

Viruses are both absurdly simple and dizzyingly complex. Many are composed of little more than a tangle of genetic material stuffed into a protein coat — not even enough for some scientists to consider them alive. They are entirely dependent on the inner workings of cells, and cannot make more of themselves without help from the life-forms they infect.
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And yet, under the right conditions, basic viral components can accomplish what many natural phenomena cannot: a process called self-assembly, combining their bits into neat, structured particles without any external forces to guide them, like cake ingredients mixing themselves into batter or snowflakes sprouting spontaneously out of room-temperature water.

It’s a beguiling question, Ms. Williams said: “Why do ordered things form without any assistance?”

Scientists can recreate this mysterious process in laboratory test tubes. They swirl together hunks of genetic material and proteins in salty chemical soup, and watch the viruses erupt forth. “It’s remarkable,” said Vinothan Manoharan, a biophysicist and engineer at Harvard University and Ms. Williams’s adviser. “You have these pieces spontaneously coming together, without any active intervention: It just happens.”

Bill Gelbart, a physical-chemist-turned-virologist at the University of California, Los Angeles, said it was this astounding buildability that drew him to viruses 20 years ago — an unexpected midcareer transition. Other diseases, like cancer, could not be boiled down to their base components and assembled or disassembled at will. Even bacteria, some of the simplest and best understood life-forms, can’t reform once ripped apart.

Viruses are different. “I was powerfully fascinated by the idea that an infectious virus particle can be made from scratch from purified components,” Dr. Gelbart said. “I think the Dr. Frankenstein in me got the better of me. I thought, ‘I have to do that.’”

That same desire has seeded dozens of virus physics labs around the globe (several of which cite Dr. Gelbart as an inspiration). Dr. Manoharan’s lab is one, focused on the assembly of bacteriophages, viruses that exclusively infect bacteria.
The Coronavirus Unveiled

Scientists around the world have captured detailed images of the coronavirus.

The static pictures and diagrams in textbooks don’t do viruses justice, Dr. Manoharan said. They tend to focus on the products of virus assembly. But the pieces within viruses — the genomes and proteins — start out as a dynamic jumble, and the chaotic motions are an obstacle for any virus that might organize itself into existence. Moreover, its components must find each other, without mistaking the cell’s cargo for its own.

By and large, researchers don’t yet have answers for how viruses solve this packaging problem. The process is especially complex for coronaviruses, which possess some of the largest known RNA-based genomes known to science. (RNA is a cousin of the DNA that encodes the human genome.)

But scientists have already figured out ways to spy on the coronavirus’s assembly process, and start to replicate it for themselves.
The New York Times