Researchers identify nanobodies that may block SARS-CoV-2

• In laboratory experiments, Australian researchers have recently identified nanobodies that block the SARS-CoV-2 virus’s connection to cells, preventing it from entering the cells.

• These nanobodies may eventually provide an alternative to conventional antibody treatments for COVID-19.

• The researchers identified a nanobody that recognized the SARS-CoV-2 virus, including emerging global variants.

• The nanobody also recognized the SARS-CoV virus, which causes SARS. This suggests that it could provide protection against that coronavirus as well.

A pair of Australian alpacas have paved the way for researchers to develop a new therapy that could block SARS-CoV-2, which is the virus that causes COVID-19, from infecting cells.

The researchers have published their findings in a new issue of the journal PNAS.

Camelids and nanobodies

Camelids — which are a group of mammals including camels, llamas, and alpacas — produce “conventional” antibodies in response to infection. They also produce nanobodies, which are smaller antibodies.

Researchers have been looking at these nanobodies as a potential treatment against COVID-19 since the start of the pandemic.

For instance, in February 2020, scientists at the Karolinska Institutet in Sweden started a study that involved injecting the coronavirus’s spike protein into an alpaca in hopes of developing a treatment to fight COVID-19.

After 60 days, blood samples from the alpaca showed that the animal had developed an immune response against the spike protein.

In the recent study, the Australian researchers immunized a pair of alpacas with a coronavirus spike protein. This did not cause the alpacas to develop disease, but it did prompt them to generate nanobodies against the SARS-CoV-2 virus.

The researchers then extracted the gene sequences encoding the nanobodies, and they used these to produce millions of nanobodies in the laboratory.

They used a Synchrotron, which is a cyclic particle accelerator, and cryo-electron microscopy, wherein they flash-froze solutions of proteins and hit them with electrons to produce images of individual molecules.

The scientists then mapped how the nanobodies bound to the spike protein and how this affected the virus’s ability to bind to the human receptor.

The researchers identified a nanobody that recognized the SARS-CoV-2 virus, including emerging global variants. The nanobody was also effective at fighting SARS-CoV, which is the virus responsible for SARS.

This suggests that nanobodies may be useful in protecting humans against other coronaviruses.

Then, the researchers injected the nanobodies adept at binding to the spike protein, either separately or in a combination of the two, into mice that they later infected with a variant of SARS-CoV-2.

They found that this nanobody “cocktail” reduced viral loads in mice with the SARS-CoV-2 virus.

“We could actually protect the mice from […] infection,” research lead Dr. Wai-Hong Tham, an associate professor at Australia’s Walter and Eliza Hall Institute of Medical Research, told Medical News Today.

A standout study

According to the researchers, this study differs from efforts by other groups looking at the impact of nanobodies on SARS-CoV-2 in two main ways.

Firstly, few studies have looked at the ability of nanobodies to prevent the virus from latching onto cells in a living organism. Most have used in vitro methods, which occur in a controlled environment such as a petri dish.

“You’re actually looking at a whole system rather than a virus on a dish,” Dr. Tham told MNT. “Obviously, there’s quite a big difference between mice and humans, but it does provide an opportunity to test the nanobodies in a more complex biological system.”

Another interesting feature of this work is that the researchers tested a nanobody cocktail as well as individual nanobodies.

“When you actually have two nanobodies or an antibody cocktail, you reduce the likelihood of viral escape,” said Dr. Tham. “So it’s just harder for the virus to make mutations that would actually stop the effectiveness of both antibodies.”

Future research

This study may lead to further investigations into treatments for COVID-19 using nanobodies. Because nanobodies are highly stable across a wide range of pH and temperature, the researchers believe that they may work well as inhaled therapies.

This type of therapy has the potential to offer humans immediate protection against COVID-19, according to Dr. Tham.

“Vaccines are amazing, right? But they do require, let’s say, a week or 2 weeks to actually have your body generate an immune response.”

This type of therapy could also benefit immunocompromised populations who are not suitable candidates for vaccination. As Dr. Tham explained, “You don’t need the person to actually mount an immune response because you’re delivering those antibodies to them.”

Written by Beth JoJack on May 4, 2021 — Fact checked by Rita Ponce, Ph.D.

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