When you think of what it takes to finally stop the coronavirus pandemic, maybe a little credit to hamsters is in order.

Yeah, the furry little critters. Seriously.

The next big weapon to fight Covid may actually be very, very tiny. It’s an aerosolized nanobody named the Pittsburgh inhalable Nanobody-21 (PiN-21), and it has proved to be extremely effective when inhaled in low doses … by hamsters.

This is the first time the nanobodies — similar to monoclonal antibodies, but smaller — have been tested for inhalation treatment against coronavirus in a pre-clinical model, University of Pittsburgh School of Medicine researchers say.

How effective are they? Well, an ultra-low dose of nanobodies reduced the number of SARS-CoV-2 virus particles in the hamsters’ nasal cavities, throats and lungs by a millionfold, compared to a placebo nanobody. The hamsters treated with the nanobodies also didn’t lose weight, which is associated with severe Covid infection.

“By using an inhalation therapy that can be directly administered to the infection site — the respiratory tract and lungs — we can make treatments more efficient,” says Yi Shi, co-senior author of a study published this week in Science Advances, and assistant professor of cell biology at Pitt. “We are very excited and encouraged by our data suggesting that PiN-21 can be highly protective against severe disease and can potentially prevent human-to-human viral transmission.”

Obviously, it’s a long way from hamsters to humans, and so much more testing has to be done. But the results so far couldn’t be more promising.

“Last April, we started to develop nanobodies, and around June to July we successfully discovered like thousands of nanobodies against SARS-CoV-2,” says researcher Yufei Xiang.

Special nanobodies from a llama named Wally helped out. Narrowing it down from 8,000 high-affinity SARS-CoV-2 nanobodies, PiN-21 was by far the most potent.

The PiN-21 nanobodies are four times smaller than most monoclonal antibodies, which provide the most effective treatment for Covid so far. Nanobodies are extremely stable, cheaper to produce and can be made quickly to adapt to a rapidly mutating virus.

“We started with hamsters because hamsters are easy,” says researcher Sham Nambulli. “They’re less expensive compared to non-human primates. And it’s always good to start with a small animal model rather than jumping to a big animal model.”

Sham Nambulli. Photo courtesy of the University of Pittsburgh.

It should be noted that these nanobodies have a different mission than vaccines. Vaccines are still the best way to stop Covid from spreading, but nanobodies can be used to treat people who are already sick, or who can’t get vaccinated for medical reasons.

“If they prefer, they can use nanobodies as a prevention, because (unlike an injection) it doesn’t hurt,” says Xiang.

This research is one of the many Covid-related projects coming in rapid succession from the University of Pittsburgh’s Center for Vaccine Research. Pitt has Biosafety Level 3 (BSL3) and Animal Biosafety Level 3 (ABSL3) laboratories, of which there are only a few across the country. So they can actually work safely with extremely infectious diseases like Covid.

“This work is the result of experts in nanobody production, infectious disease and aerobiology working closely together,” says co-senior author Paul Duprex, director of the Center for Vaccine Research.

Paul Duprex, director of the Center for Vaccine Research. Photo courtesy of the University of Pittsburgh.

PiN-21 is also effective against the U.K. variant of Covid, currently circulating widely in the U.S., notes Yufei.

“We also have other leading compounds that can combat different variants, so there’s a huge potential in the future,” says Yufei.

The next steps are obvious, and time-consuming.

“There is still a lot more to be learned before we go to clinical trials and things like that,” says Nambulli. “but this is the preliminary stage, and we are so happy that it has worked.”