UCSF scientists say they can create molecules for nasal sprays and kill coronaviruses

Synthetic antibodies, which researchers believe to neutralize coronaviruses, have been made in UCSF and could be used in nasal sprays and inhalers within months if clinical trials are successful. .. They want development to become a game changer of global efforts to stop the pandemic.

A small artificial protein molecule developed at two UCSF laboratories by a team of 60 scientists, including a PhD and a graduate student, models the super-potent antibodies found in llamas and camels.

Synthetic antibodies bind to the infamous spike protein that coronaviruses use to invade and direct human cells, according to a study published Monday as a preprint of the open access site bioRxiv (pronounced “bio-archive”). And deactivate. Peer reviewed yet.

“It’s like a mousetrap.” Peter Walter, professor of biochemistry and biophysics at UCSF and co-inventor of the AeroNab molecule, said: “It’s a big deal for us. That’s it.”

The molecule is small but more potent than antibodies naturally produced by humans in response to SARS-CoV-2, the coronavirus that causes COVID-19. In this case, they prevent the spike proteins from opening like flowers before attaching to the cells, stopping the ability of the virus to bind to the ACE2 receptor in human cells.

Walter, who is also a researcher at the Howard Hughes Medical Institute, said the formulas developed by his team are very flexible and can be dried and powdered anywhere in the world.

“They’re incredibly sturdy,” Walter said. “It’s basically an antibody, but it’s about 1/10 the size.”

It was possible to create because there were already about 2 billion different synthetic molecules, or Nanobodies, in the database, he said. The UCSF team picked the best candidates and over the last few months developed their professional version.

AeroNabs formulations are of particular value because they can be self-administered as a nasal spray or breathed in the form of an aerosol via an inhaler. He estimates that lung protection lasts about a day, so treatment must be inhaled daily. How long the nasal drops last is still unclear, but you will probably need to apply several times a day.

The idea is to protect people from COVID-19 until the vaccine is available. At least 150 potential vaccines are being studied by scientists from pharmaceutical companies, academic groups and government laboratories around the world.

The UCSF research team is discussing with pharmaceutical companies and other potential commercial partners to enhance AeroNabs manufacturing and clinical trials. If successful, Walter said the treatment could be generally available as an over-the-counter drug within three or four months.

“Their work is very exciting. It has a sound rationale. John Swartzberg, an infectious disease specialist at the University of California, Berkeley, who was not involved in the study, said: “Of course, the main thing to note is its safety and effectiveness issues… if this works, it becomes a game changer.”

Robert Siegel, an infectious disease specialist at Stanford University who is not involved in the study, said the UCSF study is an example of a pandemic-inspired innovation.

“Ultra-high affinity synthetic Nanobodies not only act in a similar way to some of the existing HIV remedies, but also some of our innate immunity to infections,” says Siegel. .. “But they offer some potential advantages in terms of delivery, manufacturing, stability, and surprising specificity.”

But he warned him not to get too excited until the new drug was validated by randomized controlled clinical trials to rule out potential side effects.

Many scientists also argued that the preprint publications were critical and that the information was preliminary and should not be taken seriously or considered definitive research.

“We’re working with AeroNabs,” said Walter, co-inventor of AeroNabs. “We’ve designed these molecules to the point where we think we are as good as we can. Our hope, our dream, is to bring the world back to normal.”