The coronavirus in a tiny drop


To better understand the journey of the coronavirus from one person to another, a team of 50 scientists created an atomic simulation of the coronavirus for the first time, embedded in a tiny drop of water in the air.

To create the model, the researchers needed one of the largest supercomputers in the world to assemble 1.3 billion atoms and track all of their movements to within a millionth of a second. This computational feat offers unprecedented insight into the way the virus survives outdoors while it spreads to a new host.

The simulated liquid drop contains the Coronavirus and be Spike proteins, long Mucilage, sticky Surfactants, and a mixture of molecules deep lung fluid.Lorenzo Casalino and Abigail Dommer, Amaro Lab, UC San Diego

“Putting a virus in a drop of water has never been done before,” said Rommie Amaro, a biologist at the University of California San Diego who led the effort revealed at last month’s International Conference for High Performance Computing, Networking, Storage and Analysis. “People have literally never seen what it looks like.”

Droplets and aerosols

How the coronavirus spreads through the air was hotly debated at the beginning of the pandemic. The traditional view held by many scientists was that most of the virus’ transmission was made possible by larger drops, often produced by coughing and sneezing. These droplets can only travel a few meters before falling to the ground.

A 3D simulation of a cough that produces both large droplets and tiny aerosols.The New York Times

But epidemiologically Studies showed that people with Covid-19 can infect others at a much greater distance. Simply speaking without masks in a poorly ventilated interior such as a bar, church or classroom was enough to spread the virus.

These results indicated much smaller drops called aerosols were important carriers of infection. scientist define Droplets greater than 100 microns, or about 4 thousandths of an inch, in diameter. Aerosols are smaller – in some cases so small that only a single virus can fit in. And thanks to their tiny size, aerosols can float in the air for hours.

A simulated aerosol that carries a single coronavirus.John Stone, Beckman Institute, Univ. of Illinois in Urbana-Champaign

Viruses cannot survive forever in aerosols, however. Researchers often find that viruses collected from the air are so damaged that they can no longer infect cells. It is possible that the air destroys the molecular structure of the virus as the aerosols evaporate. Or the chemistry in the tiny drop could become too hostile to survive.

“At this point, we don’t understand how this happens,” said Linsey Marr, a professor of civil and environmental engineering at Virginia Tech who was not involved in the new study. Microscopes that can take detailed pictures of what is going on in a virus-laden aerosol have yet to be invented.

In March 2020, Dr. Amaro and her colleagues suggest that the best way to open that black box is to build your own virus-laden aerosol.

The researchers first created a model of the coronavirus, known as SARS-CoV-2, from 300 million virtual atoms. They combined thousands of fatty acid molecules into a membrane shell and then housed hundreds of proteins inside.

A model of a coronavirus with 300 million atoms shows the viral membrane dotted with additional viral Proteins and protruding Spike proteins.Lorenzo Casalino and Abigail Dommer, Amaro Lab, UC San Diego

Some of these proteins are important because they keep the virus membrane intact. Others, so-called spike proteins, form flower-like structures that protrude far beyond the surface of the virus. The tips of the spines sometimes pop open spontaneously so that the virus can attach itself to a host cell and penetrate it.

Structure of an aerosol

After building their virus, Dr. Amaro and her colleagues found an aerosol to fill it in. From a billion atoms they created a virtual drop with a diameter of a quarter of a micrometer, less than a hundredth the width of a strand of human hair.

However, the researchers were unable to simulate the aerosol as a pure drop of water. When an aerosol dissolves from the liquid in our lungs, it brings a stew of other molecules with it from our body.

Components of a simulated aerosol: water, Mucilage, Surfactants, deep lung fluid.Nicholas Wauer, Amaro Lab, UC San Diego

This stew includes Mucilage, these are long, sugar-strewn proteins from the lining of the lungs. Aerosols also carry deep lung fluid, and Surfactants which help prevent the delicate branches of our airways from sticking together.

After the virus was loaded into an aerosol, the scientists faced the project’s greatest challenge: bringing the drop to life. Dr. Amaro and her colleagues calculated the forces acting in the entire aerosol, taking into account the collisions between the atoms and the electric field generated by their charges. They determined where each atom would be four millionths of a billionth of a second later.

In order to be able to perform these extensive calculations, the researchers had to take over the Summit supercomputer from the Oak Ridge National Laboratory in Tennessee, the second most powerful supercomputer in the world. Since the machine was in great demand, they were only able to run their simulation a few times. “We only have so many shots to see if we can actually get this thing to fly,” said Dr. Amaro.

The first run was a disaster. Tiny flaws in their model resulted in the virtual atoms crashing into each other and the aerosol bursting instantly. “It basically explodes,” said Dr. Amaro.

After half a dozen adjustment rounds, the aerosol became stable. The researchers ran the calculations again to see what was happening in the aerosol a moment later. All in all, they created millions of frames of a film that recorded the activity of the aerosol for ten billionths of a second.

“While molecular modeling is not a new thing, the scope of it is at the next level,” said Brian O’Flynn, a postdoc at St. Jude Children’s Research Hospital who was not involved in the study.

A journey through a virus-laden aerosol. Spike proteins on the surface of the coronavirus are being bombed by charged calcium Atoms. Surfactants and Mucilage are attracted to the virus’ spike proteins and can protect the virus from damage.Lorenzo Casalino, Amaro Lab, UC San Diego

The lively activity that Dr. Amaro and her colleagues observed, provided evidence of how viruses survive in aerosols. The mucins, for example, didn’t just idly wander around the aerosol. The negatively charged mucins were attracted to the positively charged spike proteins. Charged atoms like calcium fly around the droplet, exerting strong forces on molecules they encounter.

Dr. Amaro speculated that the mucins act as a protective shield. If the virus moves too close to the surface of the aerosol, the mucins push it back so it isn’t exposed to the deadly air.

“We think that it actually gets covered in these mucins and that it acts like a protective layer during the flight,” said Dr. Amaro.

Delta and Omicron

This discovery could help explain how the delta variant became so widespread. Delta’s spike proteins have a more positive charge than previous forms of the coronavirus. As a result, the mucins crowd closer around them. That attraction could potentially make the mucine a better shield.

Every now and then, one of the simulated coronaviruses flipped open a spike protein, which surprised the scientists. “The Delta variety opens up much more easily than the original variety that we simulated,” said Dr. Amaro.

A simulation of the Delta variant’s spike protein suggests that it opens wider than the original coronavirus strain, which could explain why Delta is spreading more successfully.Lorenzo Casalino, Amaro Lab, UC San Diego

Once a coronavirus enters a person’s nose or lungs, the wide opening of the delta spike can improve infection of a cell. But Dr. Amaro suspects that it is bad for a coronavirus to open a spike protein while it’s still in an aerosol, perhaps hours away from infecting a new host. “If it opens too early, it could just fall apart,” said Dr. Amaro.

Some of the molecules, which are abundant in aerosols, might be able to close the spine for travel, she said. Certain pulmonary surfactants can fit in a pocket on the surface of the spike protein and prevent it from swelling up.

Top view of a simulated spike protein.Lorenzo Casalino, Amaro Lab, UC San Diego

To test this idea and explore others, Dr. Amaro and her colleagues calculated the time frame for their simulation a hundred times, from ten billionths of a second to one millionth of a second. You will also study how the acidity in an aerosol and the humidity of the surrounding air can alter the virus.

Dr. Amaro and her colleagues plan to next build a variant of Omicron and observe how it behaves in an aerosol. They want to wait for structural biologists to figure out the three-dimensional shape of its spike proteins before getting started. But if you look at the initial findings on Omicron, Dr. Amaro already has an important quality: “It is charged even more positively,” she said.

Since Omicron’s spike proteins are even more positively charged than Delta’s, they can provide better protection against mucus in aerosols. And that can help make it even more transferable.

Three coronavirus spike proteins: the original strain, the delta variant, and the omicron variant. Omicron is more positively charged than Delta, which is more positively charged than the original stem. Over time, mutations have appeared near the tip of the spike protein positive or negative charge. Other mutations were made neutral.Fiona Kearns and Mia Rosenfeld, Amaro Lab, UC San Diego

Dr. Marr said the simulation could eventually allow scientists to predict the threat of future pandemics. They could build atomic models of newly discovered viruses and package them in aerosols to observe their behavior.

“This has implications for our understanding of new viruses that we don’t yet know about,” said Dr. Marr. “There is still a long way to go,” she said, “but this is definitely a great first step.”


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