I ts triangular spikes are what make coronavirus such a formidable foe.

But they could also be its Achilles’ heel.

Georgia College Assistant Professor of Chemistry Dr. David Zoetewey and three students are working to expose this weakness and prevent the virus’ spear-like mechanism from harpooning into human cells.

This research could someday result in a medicine that prevents coronavirus from attaching.

“Spike proteins are very important for the virus and its ability to cause infection,” Zoetewey said. “Without the spike protein, there is no viral infection. If we can do something that disrupts how the spike protein works, then we can prevent the virus from becoming infectious.”

Scientists all over the world are working on COVID-19—and the spike protein is just one small piece. Every little bit contributes to our understanding of how the virus works, however, and every step is a step in the right direction.

It’s important to not only eradicate coronavirus—but also be ready for the next pandemic.

"What made COVID-19 so bad was how fast it spreads, and that's really made it the perfect storm," Zoetewey said.

"It may not be a coronavirus next time. It may be a strain of the flu. It may be something else that we don’t even know of yet," he said, "The fact we had SARS and then MERS and now COVID-19—and they’re all coronaviruses from the same family—that tells us coronaviruses have high potential to do this again."

All viruses hijack cells. But the coronavirus known as COVID-19 is particularly cunning, because its pegs act as spears connecting it to other cells. These spikes are proteins, and proteins are built with a sequence of amino acids that dictate their particular shape and movement.

The coronavirus spikes remain folded, until a “a target is recognized,” Zoetewey said. Then, one pops out “like a jackknife” to harpoon into a victim cell—effectively taking command. The harpoon is what enables the two cell membranes to fuse together.

“Obviously, this is a really big complicated protein,” Zoetewey said. “The function of the spike protein is to attach to the cell it’s going to be infecting. The contents of the virus get dumped inside. And, so now you have this RNA that goes inside the cell, and the RNA contains the instructions to make new viruses and cause infection. That’s its only purpose.”

Scientists know what the spike protein looks like before and after the harpoon effect. But they can only speculate on what occurs in between.

Proteins are so small that even the wavelength of invisible light is much bigger, Zoetewey said. A researcher in China was able to determine the structure of a small piece of the spike protein—called a “coiled-coil”—in 2020 by using X-ray crystallography. From that, Zoetewey noticed he’d seen this kind of coiled-coil before as a doctorate student at the University of Colorado in the early 2000s.

At that time, another outbreak had occurred: Severe Acute Respiratory Syndrome (SARS). It had a higher fatality rate than COVID-19 but was quickly contained and died out. Zoetewey’s lab collaborated with an expert in coronaviruses, who identified the coils as a “critical piece” of the spike protein.

When COVID-19 spread globally in early 2020, Zoetewey recalled the coiled-coil as “the linchpin to the coronavirus’ infectious mechanism.” He realized his students could work on this small piece of the puzzle and discover how spikes unfold and thrust into cells.

Freshman chemistry major Gabe Allred of Eatonton said he was amazed to be doing undergraduate research his first year in college. Even more remarkable, he's doing research on a virus that’s currently challenging the entire world population.

“I always knew it was a dangerous virus," Allred said, "but it wasn’t until I joined Dr. Zoetewey's group that I learned what makes it dangerous, and how exactly it spreads from cell to cell and replicates. This was a very fascinating insight to learn about a very prominent problem.”

As a first-year student, it’s Allred’s job to learn the fundamentals of research and procedures of the coronavirus project. In future years, he’ll be stepping into a leading role. But, for now, he shadows two upperclassmen in the lab to learn all he can.

One is sophomore chemistry major Caylee Durden of Statesboro. She chose Georgia College for its research opportunities. Her role is to grow and separate the spike protein.

“Although I knew research was available to undergraduates,” Durden said, “I didn't know it’d be something this exciting and relevant to today's world, which I think makes it even more interesting and meaningful to me.”

Students are not working with the actual coronavirus—just little pieces of the spike protein created from a sequence of amino acids. Spike proteins are made from a chain of 1,300 amino acids. Zoetewey’s team is looking at about 100 of these, which make up two separate coiled-coil regions from the spike’s stem.

These amino acids are an instructional code given to bacterium, where the proteins can be grown in the lab.

Once Zoetewey’s team is able to grow these spike protein fragments in large batches, students will separate them from the bacterium. This is Durden’s job. She mixes a “nickel solution” inside test tubes that look aqua in color. Their specific protein attaches to nickel. When another chemical is added, everything washes away except the protein.

The group has worked all semester to set up this isolation protocol and catalogue the steps. The next phase would involve a Nuclear Magnetic Resonance machine (NMR), which Zoetewey hopes to purchase with a collaborative grant from the National Science Foundation (NSF). The machine will take pictures of the spike protein in its native state and provide “a living picture” of its movement and function.

Each NMR picture looks like a “spectrum of dots”—basically individual atoms that tell researchers how proteins interact with one another and create movement.

It’s “a long game of connect-the-dots,” Zoetewey said. With help from a colleague at the University of Oklahoma, who has a stronger NMR, he hopes to learn how the spike unfolds and harpoons.

“The ultimate outcome is way down the line,” Zoetewey said. “By looking at the way all these atoms interact with each other, we can potentially design a molecule that would prevent the harpoon interaction from taking place.”

“If we keep it from attaching, the coronavirus would just sit there and eventually come back off,” he said. “It wouldn’t be able to do anything. The RNA would never get inside the human cell. It’d probably circulate for a while until it’s recognized by your defenses as a foreign invader and your body would just clear it out.”