Standing in front of a cage full of mice, in full protective gear, Gunnar Gottschalk didn’t know which mice had received an experimental COVID-19 treatment and which had not.
What he knew was that all of the mice, except those in the control group, were injected with an inactivated, or non-infectious, version of the new coronavirus.
Some of the mice died right away. Others huddled together in the corner of the cage, shivering and hunched over. Those mice weren’t burrowing, grooming or socializing like they usually would.
“They really couldn’t walk,” he said.
But some of the mice were completely fine. Those mice had received the experimental, preventative COVID-19 treatment made by Arizona biotech company Sotira, where Gottschalk works as a principal scientist.
“It was truly incredible to see this,” Gottschalk said. “I just knew at that point that we had something.”
The treatment, called KEPTIDE, is a nasal spray that works by stopping the virus from attaching onto and entering cells. Studies done in mice, primate cells, and human lung cells have all been promising so far, the company said, showing 100% effectiveness with no negative side effects.
One hitch: The treatment won’t offer long-term protection. Its effects could work for only about a day and looks most promising for short-term uses.
And it won’t be able to offer protection to consumers anytime soon. The product still needs to be tested in humans and is a long way from being sold in stores or administered in health care settings.
The company is currently waiting for FDA approval to start formal clinical trials for the treatment in humans. If KEPTIDE is just as effective and safe in humans as it was in lab tests, the treatment could help prevent the spread of COVID-19 and function as an alternative for people who are unable to access vaccines or who are distrustful of them.
Already, logistical challenges have emerged around the distribution and administration of COVID-19 vaccines. But unlike vaccines, the KEPTIDE treatment would be cheap and easy to make, and doesn’t require cold storage, easing distribution concerns. And instead of going to a doctor’s office, Sotira CEO James Keating said this treatment could theoretically be sold as an over-the-counter or off-the-shelf medication, depending on future tests, FDA approval and regulatory decisions.
“What we believe we have here is something that you could purchase at a pharmacy…and you can store and use as needed,” Keating said.
In pre-clinical tests, Sotira scientific director Avik Roy said the protective effects of the KEPTIDE started 30 minutes after the treatment and lasted for up to 24 hours. He believes that the effects may last longer in human trials, but exactly how long it would protect humans is still unknown.
The idea is that first responders could take the treatment before starting a shift at work, he said, or ordinary people could take the treatment before gathering socially.
“It could have a huge impact in society,” Roy said.
Treatment works ‘like a shark net’
When Roy started designing the treatment in March, he had little information about the novel coronavirus. He didn’t even know what the exact structure of the virus was.
So he used a related coronavirus, which causes Severe Acute Respiratory Syndrome, or SARS, to design the treatment. The virus is very similar to the novel coronavirus and also has a spike on the outside to attach to and infect cells.
With this model, Roy came up with a modified molecule called a peptide. Peptides are short chains of amino acids, the natural building blocks of life. Since the treatment is made of natural substances and not synthetically-made substances, Keating believes it is safer.
“There’s less chance of adverse reactions,” he said.
Roy designed this particular peptide to block the spike on the novel coronavirus from attaching to its primary receptor, called the ACE-2 receptor. Normally, the ACE-2 receptor is like a lock that the virus’s spike unlocks to enter a cell and infect it.
But Roy couldn’t block the ACE-2 receptor entirely. The ACE-2 receptor is found in a variety of organs, such as the lung, kidney, heart and intestines, and is important for the regulation of blood pressure and fluid balance in human bodies.
“If somehow this receptor is modified or dysfunctional, or it doesn’t work properly, then you will end up having all different kinds of diseases, starting from diabetes, to obesity, cancer and all these things,” Roy said.
Instead of blocking the receptor entirely, the peptide Roy invented works like a shark net. It allows ocean water and small fish — normal nutrients and molecules — to go through the ACE-2 receptor, but blocks sharks — the virus — from getting through.
If the virus cannot enter cells, it just floats around the body harmlessly until the body kills it or it dies.
‘I think we have something here’
Once Roy came up with the modified peptide, his colleague, Gottschalk, approached the company’s CEO.
“We sat down in my garage and he said, ‘I think we have something here and we should pursue it,'” Keating recalled. “At that point, it was going to cost us $15,000 to pursue it.”
Despite the financial risks and the fact that Sotira is a small four-person company, Keating decided the company would give the treatment a chance.
Since then, the costs and time commitment of developing the treatment have ballooned, according to Keating, but the results have been rewarding.
“The science has been so sound and so good that it’s worked out,” Gottschalk said. “And that’s why I think even as we take on this next climb of Everest through the FDA regulatory process and everything else … everyone’s just gung-ho.”
Pending FDA approval, the company hopes to start human trials in the spring of 2021. Meanwhile, pharmaceutical companies are gearing up for possible COVID-19 vaccine distribution late this year and early next year, pending FDA approval.
But not everyone might agree to take the vaccine, due perhaps to concerns over unknown long-term impacts, distrust or anti-vaccination sentiment. A poll for the Associated Press-NORC Center for Public Affairs Research found that 20% of respondents would refuse to take a vaccine if one is approved, and another 31% were unsure.
Keating’s hope is that those who opt out of a vaccine could use this treatment to stay safe and stop the spread of COVID-19.
“This is an entirely different approach that will appeal to a lot of people who simply aren’t comfortable with with a vaccine driven treatment,” Keating said.
KEPTIDE is also cheaper to make and would likely cost much less than a vaccine.
The company still has a long way to go before KEPTIDE would be available to the general public, a road that includes getting FDA approval and figuring out large-scale manufacturing facilities or potential partners to help manufacture the treatment on a massive scale.
Since it’s unclear whether vaccines provide long-term protection against COVID-19 and unknown how many people will get vaccinated right away, Keating, Roy and Gottschalk think this treatment will still play an important role in managing the pandemic, even if it is released much later than COVID-19 vaccines.
“Coronavirus is not going anywhere,” Roy said. “It will be here for a long time.”
He also believes the nasal spray could be used as a treatment for those already suffering from COVID-19, and that it would be more effective than current anti-viral drugs.
‘Something beyond a virus’
One of the more astonishing findings of Roy and Gottschalk’s research for Sotira was the discovery that even though the mice in their experiment had been given inactivated, or non-infectious versions of the novel coronavirus, 28% of the non-treated mice still died, and the other non-treated mice suffered symptoms of an infection.
To inactivate the virus, researchers disable the genetic components that are normally responsible for making the virus replicate inside a body. Theoretically, injecting inactivated virus into mice should not have caused sickness.
“The novel coronavirus is something beyond a virus,” Roy said. “Even if you inactivate the virus, it’s still able to kill the subject.”
Both Roy and Gottschalk believe that part of the novel coronavirus’s disastrous impacts may have something to do with the actual attachment of the virus to the ACE-2 receptor.
“It’s actually physical interaction between these two that causes a lot of the downstream effects,” Gottschalk said.
These downstream effects include the release of inflammatory signals in the body called cytokines. In many severe cases of COVID-19, the body’s immune system overreacts and releases too many cytokines, which can cause inflammation, organ damage, fluid-filled lungs and even death.
It doesn’t take much virus to cause such reactions, Gottschalk said, and often the cause of severe symptoms has less to do with the virus itself, and more to do with inflammatory responses.
Sotira’s findings may help explain why some antiviral drugs and treatments have failed to deliver on their promises of treating COVID-19. Any treatment that targets the genetics, or infectiousness, of the virus is not likely to fix the problem, according to Gottschalk. The company’s findings suggest more effective treatments would block the virus from attaching onto the ACE-2 receptor in the first place.
Though KEPTIDE is still a long way away from hitting shelves, the company believes the technology behind it could also work against other types of coronaviruses, such as the common cold, SARS or future related viruses that haven’t yet infected humans.
“This approach is sort of a novel mechanism to address this particular pandemic and perhaps those that will happen in the future,” Gottschalk said.
Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environment. Send her tips, story ideas, or dog memes at firstname.lastname@example.org and follow her on Twitter @amandamomorris for the latest bioscience updates.
Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.
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