Pitt virus therapy ‘shows promise’

Possible COVID-19 treatment could be used as an inhalant

Researchers at the University of Pittsburgh School of Medicine have developed a potential COVID-19 therapy from llama "nanobodies" that lab tests show is "orders of magnitude" more powerful against the virus than antibodies from people who have recovered from infection.

The researchers will be working through trials in hopes of producing a medication that could be manufactured and distributed easily and used as an inhalant to both prevent and treat the disease.

The tiny, single-chain nanobodies have a "perfect structure" that enables them to bind to and disable the coronavirus, attaching to the virus' spikes, so the virus can't connect to a human receptor cell, according to Assistant Professor of Cell Biology Yi Shi, who spoke on a Zoom call with reporters this week.

The researchers have developed "several different flavors" of the nanobodies to help ensure that mutations of the virus wouldn't allow it to "escape" being neutralized, Shi said.

"Like a Swiss Army knife," he said.

The therapy could be used as an inhalant because the nanobodies are sufficiently stable not to break down when aerosolized, according to Shi.

Inhalation therapy is less expensive than intravenous therapy, according to the researchers.

Also helping to keep down the cost and increase "access" are the ease of duplicating the amino acid sequences for the nanobodies by using microbes in manufacturing, plus the resulting medication's being storable for six weeks at room temperature, researchers said.

The researchers found the nanobodies by using a mass spectrometry technique that Shi had developed over the past three years.

He used the technique on the blood of a llama -- "Wally" -- that had developed those nanobodies after being immunized with a piece of COVID-19 spike protein.

The researchers used a llama, because like other camelids -- but unlike other mammals, including humans -- they produce single-chain antibodies, Shi said.

The nanobody is the "warhead" of the antibody, according to Shi.

It took two or three months to discover the "ultra-potent" versions that are the basis for the proposed therapy, he said.

A fraction of a nanogram of those nanobodies neutralized enough virus to spare a million cells from being infected, according to a Pitt news release.

It could be "the most potent biologic" to date, Shi said.

The researchers are exploring now "how well it will work, not just in plastic dishes," said Paul Duprex, director of Pitt's Center for Vaccine Research, who also spoke to reporters.

That will entail going through Phase 1, 2 and 3 trials, Duprex said.

"The results are really very promising," he said.

The expected arrival of a vaccine in the coming months doesn't mean that such therapies won't be needed, Duprex said.

"It's really good to have multiple ways" to fight COVID-19, Duprex said.

A spray containing the nanobody might be used as an ad hoc intervention if someone is about to encounter an infection risk or has just encountered one, Duprex said. "Ready, armed and able to neutralize," he said, in response to a suggestion that a user could slip a spray bottle of the proposed medication in a pocket before going out for the evening.

The researchers published their findings in the journal Science this week.