A combination of cloud computing and scientific ingenuity could change how we fight COVID-19 and its variants, such as a nasal spray used at the earliest stages of infection.
By Justine Brown | July 2021
The rollout of COVID-19 vaccines was a huge step forward in the battle against a virus that’s caused more than 3.7 million deaths worldwide as of June 2021, according to the World Health Organization. But experts predict coronaviruses will continue to mutate, and that containing these variants will be an ongoing fight for years to come.
For that continuing fight, we’ll need COVID-19 treatments for people who get the disease, as well as vaccines to prevent it. And that’s where a “pocket” in the COVID-19 virus comes in, a weak spot in the virus that researchers at the University of Bristol believe can be targeted with drugs to stop the disease at the first sign of infection.
“The aim of our treatment is to significantly reduce the amount of virus that enters the body and to stop it from multiplying,” says Professor Imre Berger, director of the Max Planck-Bristol Centre for Minimal Biology at the University of Bristol. “Then, even if people are infected with the virus or exposed to it, they will not become ill because the antiviral prevents the virus from spreading to the lungs and beyond. Importantly, because the viral load will be so low, it will likely also stop transmission.”
“Working with Oracle, we figured out how this immensely intensive type of computation can be done much faster than had been possible before—literally within hours and days.”
Berger, along with Professor Christiane Berger-Schaffitzel from the School of Biochemistry and other researchers at the University of Bristol, are focusing their work exclusively on SARS-CoV-2, the virus that causes COVID-19. They’ve created a biotech startup, Halo Therapeutics, with plans to create drugs that exploit this “pocket” in the virus. Using a combination of Oracle high-performance cloud computing and scientific ingenuity, the team could change how we fight COVID-19 and its variants.
In the lab, Schaffitzel and Berger centered their work on the way COVID-19 is triggered by its spike protein. Computational modeling of SARS-CoV-2 was critical to this discovery. Schaffitzel and Berger collaborated with Oracle for Research, which supported the team with a one-year Oracle for Research grant. The grant provided free access to Oracle Cloud Infrastructure’s high-performance computing capabilities to process very large datasets from the university’s powerful cryo-electron microscope, which allowed the scientists to create a high-resolution, 3D digital model to visualize and study the spike protein molecule’s composition.
“That was easier said than done because we were collecting literally terabytes worth of data, and in order to piece it all together, we needed massive computation,” says Berger. “It used to take weeks and months to get this done. Working with Oracle Research, we figured out how this immensely intensive type of computation could be done much faster—literally within hours and days. Speed is everything in a pandemic, and our colleagues at Oracle made things happen at an incredible pace.”
Studying their model, Schaffitzel and Berger then found something unexpected: The spike’s pocket appeared to bind to linoleic acid, a key molecule in the body that regulates inflammation and immune response. Even more exciting was the realization that the spike exists in two different shapes—an open form and a closed form. The open form allows the virus to replicate and create a chain reaction. The closed form is not infectious. In other words, if the pocket contained in the spike protein could be closed, the virus could be rendered harmless.
“That told us that we had something amazing in our hands,” Berger says. “We had this pocket, which is like a lock. And we could apply this lock to arrest the virus in a noninfectious form and prevent it from penetrating cells in the nose, throat, and lungs.”
The team published a study of their findings in fall 2020. Since then they’ve translated their research into a range of therapeutic antiviral products and launched Halo Therapeutics to bring them to market. The company’s first proposed product, now being prepared for clinical trials, is a nasal spray to target the zone where the virus invades the body.
“First the virus goes into the nose and starts to replicate—that’s the first ‘hot zone.’ A few days later, it slides into your throat, and then into your lungs. That’s when mayhem starts,” Berger says. “To stop COVID-19 you need to catch the virus as early as possible. That’s why we decided to focus on the nasal spray first, which can be used to treat people immediately when they feel they have possibly contracted the virus.”
The hope is that the spray can stop COVID-19’s advance and spread. The company is also working on an asthma-type inhaler to target the lungs of people who fail to catch the virus with the nasal spray.
If approved, Halo Therapeutics’ antivirals could be used by patients globally at the first sign of COVID-19 symptoms, or when they have been in contact with someone with the virus, preventing the virus from taking hold and stopping further transmission. The clinical trial process can take many months, and often years, and there’s no guarantee even a promising proposed treatment will make it through regulatory approvals. But the Halo Therapeutics team is encouraged by the lab studies, including work that suggests such antivirals would be effective against all known pathogenic coronavirus strains, including the highly contagious current variants.
“Our vision is that at the first sign of the disease, whether you come into contact with someone who has COVID-19 or you have early symptoms, you would self-medicate at home to stop the virus in its tracks and prevent you from getting ill,” says Schaffitzel.
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