UCSF scientists turn to llamas for new drugs for coronavirus

The wonder of a vaccine is its power to infect the COVID-19 virus.

But a new class of anti-drugs could do that too – faster. While faxes work days or weeks to work, the new medications could help within hours.

Armed with a growing understanding of human immunity, Bay Area researchers are producing these potential treatments based on antibodies, the small Y-shaped molecules that have been proven to protect against infection and disease.

“Basically, this is the preferred system of the nature of drugs,” said immunologist Jacob Glanville, whose startup in Southern San Francisco based Distributed Bio Computers and technology used to make lab-grown antibodies.

On Tuesday, UC San Francisco scientists discovered their own antibody-inspired product, called “AeroNabs,” that can even be controlled by a nasal spray or inhaler. Although not yet tested in humans, it does show potent antiviral properties.

In a global race involving hundreds of drug companies and academic labs, the goal of antibody research is to block the virus from infecting cells.

There are still some major unknowns. Which antibody-like products are most effective? Can they be made cheaply, and in bulk? Do they persist, or do they disappear quickly?

But based on promising preliminary data in the lab and in animals, teams are now expanding tests, and early results are expected by the end of the summer. If successful, these therapies can be used to help those at high risk of becoming infected or who are already infected, even seriously ill.

“This is a very important innovation at a practical, preventive level,” said Dr. Barry Bloom, professor of public health and former dean of the Harvard TH Chan School of Public Health.

The field of antibody-based therapy builds on concepts from two related fields: vaccines and the so-called ‘convalescent plasma’.

Vaccines work because they provoke your body to produce antibodies. But it can take weeks after a vaccination is given for a person to develop protective antibodies. And some people, such as parents and immunized compromise, have weaker natural immunity, so are not always helped by a vaccine. And a successful vaccine against COVID-19 will not be ready until late autumn, at the earliest.

“Convalescent plasma” works with other people’s anti-antibodies – the ones that have been restored. It also has disadvantages. Plasma is a soup of many things, not just antibodies. There is not enough to treat everyone. And its use is inefficient, with a complicated collection and distribution process.

What would happen, scientists asked, if we were to sidestep all of this and instead just create a custom-designed anti-body product in the lab?

Faster than a vaccine and more efficient than convalescent plasma, it acts as a targeted missile. And unlike the drugs Remdesivir and Dexamethasone, it causes few side effects and can be used before serious illness.

The UCSF effort – led by two of its most promising scientists, biophysicist Peter Walter and protein engineer Aashish Manglik – turned her to the animal kingdom for her project. They have introduced an unlikely species – llamas – that have small antibodies that are known to prevent coronavirus infections.

The llama antibodies, called nanobodies, have special properties. They are so small that they are very capable of binding to the “spike protein” that the virus uses to attach to cells. They are also structurally stable, which can reduce their delivery directly to the lungs, via an inhaler. They can be mass-produced by bacteria, a step that could accelerate cheap production.

After isolating the key gene sequence from the nanobodies, the UCSF team manipulated a product that prevents the COVID-19 virus cells from entering lab experiments. Now they are talking to pharma companies to increase production and clinical trials.

If these tests are successful, the scientists aim to make AeroNabs widely available as a cheap, over-the-counter medicine. Because the product acts quickly, it can help people who are newly exposed or who work in high-risk institutions, such as health care workers.

The aerosol is not the only antibody effort. San Francisco-based Vir Biotechnology has found antibodies in COVID-19 survivors and modified the antibodies in the lab to increase their potency and longevity. It is partnering with pharmaceutical giant GlaxoSmithKline to launch a clinical trial of its lead candidate later this month, called VIR-7831.

At Distribus Bio, scientists used computers to model billions of possible variants of antibodies against a related coronavirus. Of these, it has constructed five with potential utility against COVID-19 – and is now testing one. To date, this product has prevented viral infection in healthy hamsters. And in lungs of diseased hamsters, it reduced symptoms dramatically.

Other major projects are underway at Regeneron Pharmaceuticals, AbCellera, Eli Lilly, AstraZeneca, IDBiologics and Ology, among others.