An alpaca nanobody blocks Sars-CoV-2 infection

Hyperaxion Sep 5, 2020

Scientists found that the particles bind to the spike protein in the new coronavirus, preventing it from entering human cells.

Researchers at the Karolinska Institutet in Sweden have identified a small neutralizing antibody, called a nanobody, which has the ability to block the entry of Sars-CoV-2 into human cells.

The discovery was recently published in the journal Nature Communications.

The Tyson alpaca.
The Tyson alpaca. (Credit: PreClinics).

The first stage of the research

In February, scientists injected the spike protein, used by the new coronavirus to enter cells, in an alpaca.

According to the scientists, after 60 days, blood samples from the animal showed a strong immune response against the spike protein.

“We hope our findings can contribute to the amelioration of the COVID-19 pandemic by encouraging further examination of this nanobody as a therapeutic candidate against this viral infection,” said corresponding author Gerald McInerney, who is a professor of virology at the Karolinska Institutet.

Ty1

After the success of the first stage, the scientists cloned, enriched, and analyzed sequences of B-cell nanobodies, a type of white blood cell, to determine which particles were most suitable for further study.

They realized that one of them in particular, Ty1 (named after the alpaca, called Tyson), neutralizes the new coronavirus.

That’s because Ty1 binds to the part of the spike protein responsible for connecting to the ACE2 cell receptor, used by Sars-CoV-2 to infect cells.

Three Ty1 molecules binded to the spike protein.
Three Ty1 molecules binded to the spike protein. (Credit: Martin Hällberg)

As the receptor is “occupied” by the nanobody, the pathogen is unable to enter the cell and, thus, the infection does not occur.

“Using cryo-electron microscopy, we were able to see how the nanobody binds to the viral spike at an epitope which overlaps with the cellular receptor ACE2-binding site,” said Leo Hanke, co-author of the research. “[This provided] a structural understanding for the potent neutralisation activity.”

Nanobodies

Nanobodies are fragments of antibodies that occur naturally in the camelid family, which includes animals such as alpacas, llamas, and dromedaries, and can be adapted for humans.

Nanobodies offer several advantages over conventional antibodies as candidates for specific therapies, as they are less than one-tenth the size of conventional antibodies and are usually easier to produce cost-effectively.

In addition, they can be safely adapted to humans and are proven to be effective in helping to treat viral respiratory infections.

“Our results show that Ty1 can bind potently to the SARS-CoV-2 spike protein and neutralize the virus, with no detectable off-target activity,” explained Ben Murrell, one of the scientists.

“We are now embarking on preclinical animal studies to investigate the neutralizing activity and therapeutic potential of Ty1 in vivo.”

Related topics:

Alpaca Coronavirus Covid-19

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