As the world waits for a vaccine to help bring about the end of the coronavirus pandemic, scientists in Northern California have been at work on a different approach — one that takes cues from llamas and their unique antibodies.
Llamas, like all mammals, have antibodies that protect them from viruses. But llama antibodies are different — they're tiny. Their diminutive stature gives them the unique ability to bind to proteins on the outside of the coronavirus that are crucial to its spread.
Now, scientists say they hope to harness the power of llama antibodies to stop the coronavirus from infecting humans. At the University of California, San Francisco, researchers created a lab-made molecule inspired by llama antibodies that they say is surprisingly effective at neutralizing the coronavirus.
"It binds to the virus' spike protein with an unmatched affinity — we've never seen anything like this in my lab before," said Peter Walter, a molecular biologist and biochemist who is part of a team working to develop a potential coronavirus treatment using the llama-inspired compound. "It was absolutely beautiful to see."
Don't put the cart before the llama — Walter and his team of researchers have a long way to go before any treatments are ready for use. But his work highlights how the scientific community is drawing on a wide range of recent discoveries to create ways to fight the coronavirus — most of which have never been used before.
In London, scientists are experimenting with small pieces of RNA to jump-start the immune system. Researchers in Syracuse, New York, are evaluating the safety of treating patients with antibodies from genetically engineered cows. Another group is looking at alpaca antibodies. And others are investigating whether patients who were asymptomatic or had only mild symptoms have something in common that could play a crucial role in developing treatments or a vaccine.
Walter and his team are building on discoveries that are just a few years old. Xavier Saelens, a virologist at Ghent University in Belgium, who isn't involved with the UCSF project, has been studying llama antibodies since 2016 to develop potential treatments for other known coronaviruses, such as SARS and MERS.
In lab tests, Saelens found that the llama antibodies that could protect against severe acute respiratory syndrome, or SARS, were also able to block the coronavirus that causes COVID-19. The findings were published in May in the journal Cell.
Saelens said that he hopes the antibodies have prophylactic applications but that more research will be required. A clinical trial is being planned and could proceed before the end of the year, he added.
The UCSF project, dubbed AeroNabs, goes a step further by taking inspiration from llama antibodies to produce lab-made versions that function similarly to fight infections. The hope is that the synthetic molecules could be administered as a nasal spray or with inhalers as an early intervention to keep newly diagnosed patients from getting seriously ill or as a preventive measure to stave off infections altogether.
"We have this period where an inhalable drug that can catch the virus before it ever enters the cells could provide a bridge or a stopgap measure to help until an effective vaccine can provide a long-term solution," Walter said.
The engineered molecule works by binding tightly to viral proteins from the spikes that coat the outside surface of the coronavirus. Because viral proteins can bind only to certain other proteins in the human body — similar to a lock and a key — the synthetic compound essentially runs interference and prevents the virus from infecting cells.
The researchers designed the molecule to mimic how llama antibodies function.
"The idea is we want to take the tiny architecture of antibodies found in llamas and try to recapitulate what's normally found in these animals, but synthetically," said Dr. Aashish Manglik, a structural biologist at UCSF, who co-led the research with Walter.
The molecules are stable enough to be made into a dry powder and aerosolized, which means the antibodies could be administered at home through a nasal spray or with a nebulizer similar to what's used to treat asthma patients. Additional research is needed to test how long the protection lasts, but Manglik estimated that the nebulizer approach would likely need to be used daily.
He said the treatment could be most effective as an early intervention, given to patients shortly after they are diagnosed with COVID-19. That type of early approach could prevent some patients from developing severe symptoms or needing hospitalization.
Preliminary results of the UCSF research were posted this month to the preprint server bioRxiv, and the findings haven't yet been peer-reviewed.
Sheena Cruickshank, an immunologist at the University of Manchester in England, who wasn't involved with the research, called the results "interesting," but she added that the project is a long way from being ready for clinical trials.
"More investigations are needed to validate it and confirm it will work in the body and to see how durable it will be," she said.
Cruickshank said the llama-inspired antibodies show promise as a tool to fight infections, but she raised concerns about whether the synthetic molecule would itself be seen as a foreign intruder, triggering the body's immune system against it.
Walter said he and his colleagues tried to prevent that by "humanizing" the molecule, a process that kept the scaffold of the molecule intact but then "made it look like a protein that naturally occurs in humans."
The researchers recognized the need for more research and added that they hope future tests will be able to investigate the molecule's safety and its effectiveness in humans.
"We think the probability of any safety concerns is low, but it's critical to do safety studies, because you can't anticipate everything," Manglik said.
Walter said he is also acutely aware of the need to temper expectations, particularly in a highly politicized climate in which misinformation about the coronavirus and potential treatments can proliferate wildly.
"I feel pressure to move effectively forward and fast, because we have over 5,000 people dying every day, so any day lost is measurable in death," he said. "But on the other hand, we don't want to overpromise."
Still, he hopes his project, and others like it, will give people hope that scientists are working hard to find a solution.
"I hope it shows that we're doing our best to try to help humanity and society come back to some state of normalcy," Walter said. "But does it make me nervous? Of course."