Researchers at the University of California, San Francisco, reported Tuesday that they have formulated a nasal spray that can help remove the coronavirus. They are working with business partners to produce and clinically test it.
They call the aerosol AeroNabs. It is not a cure, but it is an antiviral that aims to prevent COVID-19, the respiratory disease that has killed hundreds of thousands worldwide.
“Much more effective than forms of personal protective equipment, we think of AeroNabs as a molecular form of PPE that can serve as an important stop until vaccines provide a more permanent solution to COVID-19,” he said. AeroNabs inventor Peter Walter, professor of biochemistry and biophysics at UCSF.
UCSF graduate student Michael Schoof led a team of researchers who developed a synthetic molecule that places a close mechanism on mechanisms within the virus that allow it to infect human cells. In a new paper, Schoof and company set out experiments in which they used live virus to show that their man-made molecule is among the most potent antivirals yet against the coronavirus, scientifically known as SARS-CoV-2.
“We have assembled an incredible group of talented biochemists, cell biologists, virologists and structural biologists to take the project from start to finish in just a few months,” said Schoof, a member of Walter Laboratory and co-inventor of AeroNabs .
He and Walter said they were inspired by antibody-like immune proteins, called nanobits that occur naturally in bulbs, camels and other related animals.
Dr. Aashish Manglik, an assistant professor of pharmaceutical chemistry, often uses nanobodes in his research on the structure and function of proteins that send and receive signals across cell membranes. He is also a co-inventor of AeroNabs.
“Although they function much like the antibodies found in the human immune system, nanobodes offer a number of unique advantages for effective therapy against SARS-CoV-2,” he explained.
Smaller than human antibodies, nanobodes are easier to manipulate and modify in the laboratory environment, UCSF scientists said, and they have a simple structure that also makes them more stable. This also makes them easier and less costly for mass production, giving them another advantage over human antibodies.
Scientists set up genes that contain molecular schemas to build nanobots in E. coli or yeast, and these microbes become high-yield nanobode factories. The scientists then use protein engineering to develop those nanobodies into the synthetic molecule in AeroNabs.
The key, they said, was to prevent so-called spike proteins on the surface of the coronavirus, allowing the virus to jump into receptors on other cells and enter them. These spikes also give the virus a crown-like appearance when viewed through an electron microscope, and that is why this family of pathogens is known as the “coronavirus”.
Once the virus has attached to the ACE2 receptors on other cells, it then turns its host into a coronavirus producer. UCSF researchers sought nanobodies that could prevent interactions between coronavirus stem proteins and human cell ACE2 receptors.
They carefully reviewed a library of more than 2 billion synthetic nanobodes recently developed at the Manglik lab, identifying 21 nanobodes that could close the point-receptor interaction.
They then turned to a scientist in France to determine if the nanobodes worked: Veronica Rezelj, a virologist at Marco Vignuzzi’s laboratory at the Pasteur Institute in Paris, tore down three promising nanobodies against live SARS-CoV-2 and found them be powerful, preventing infection even at extremely low doses.
The most powerful of these nanobodes not only placed a shear on the spike protein binding mechanisms, but also acted as a molecular mousetrap, tightening at the tip while it was in its closed, inactive state. Researchers like that this added another layer of protection against ACE2 peak interactions.
Still unhappy, the scientists did other experiments that allowed them to find other ways to mine SARS-CoV-2. A triple bonded nanobode was 200,000 times more powerful than each of the single nanobodes.
“They put together two modified nanobits, and it was so effective that it exceeded our ability to measure its potency,” Walter said.
“We are not alone in thinking that AeroNabs are an extraordinary technology,” Manglik said. “Our team is in ongoing discussions with potential trading partners who are interested in the production and distribution of AeroNabs, and we hope that human trials will begin soon. If AeroNabs proves to be as effective as we anticipate, they can help reshape the course of the worldwide pandemic. “
They did not provide a timeline when AeroNabs could be ready for the market, but in announcing the product, they said they envision it as a solution that can be used at least until a vaccine is approved. And, it will continue to be useful for people who cannot get into a vaccine or do not respond to them.
They said they anticipated that every product would be widely available, cheap and sold at the counter.