A llama in front of the Machu Picchu archeological site in Peru. Photo: Alexandre Buisse / Wikimedia Commons

Israeli and American researchers have developed a cocktail of microscopic nanobodies that were found to neutralize the coronavirus in animals and were highly resistant against mutations found in variants, including Delta.

The new preclinical study — conducted by research teams led by American researcher Yi Shi of the University of Pittsburgh and Dr. Dina Schneidman of the Hebrew University’s School of Engineering and Computer Science, published this month in the leading journal Nature Communications — found three mechanisms by which the nanobodies can disarm the virus, block it from infecting cells and prevent the onset of the disease.

The researchers believe that the findings could serve as guidance for the development of future vaccines and therapeutics that may work against a wide variety of coronaviruses, including variants not yet in circulation.

“Finding these mechanisms is of huge importance in preventing the virus from entering cells not only for existing variants and those that can appear in the future, but also for other viruses of the corona family, which may develop into similar global diseases in the future,” explained Tomer Cohen, who is part of Schneidman’s research group at Hebrew University.

To generate the nanobodies, the researchers used llamas at an alpaca farm in Massachusetts, vaccinating a black llama named Wally with a piece of SARS-CoV-2 spike protein; two months later, the animal’s immune system produced nanobodies against the virus.

The choice of llama was no coincidence: all camels produce antibodies similar to humans, along with smaller antibodies, about half the molecular weight of human antibodies. These small antibodies were found to be able to reach areas inaccessible to large antibodies like those produced by humans, and they also proved to act more effectively. The researchers’ complex task was to identify within the antibodies found those with the highest effectiveness to neutralize the coronavirus.

For now, the cocktail of nanobodies cannot yet be applied, as the study still needs to pass the clinical trials stage.

“The results of the study on the nanobodies continue to be promising, we are halfway through but certainly see that there is hope on the horizon. Such approvals take time,” Schneidman said. “If we can produce an innovative drug through the cocktail, it will be a treatment that can save lives — if given early on in the disease outbreak to patients. In addition, anyone exposed to verified patients will also be able to use this treatment as a preventive treatment.”

During a three-month study, the researchers produced thousands of nanobodies for SARS-CoV-2 spikes with the ability to neutralize the virus at very high rates. Using computational methods for structural modeling developed in Schneidman’s group at Hebrew University, the researchers mapped the exact location of each nano-antibody over the spikes of the coronavirus. The precise structural mapping of the nanobodies produced in animals enabled the engineering of a new nanobody cocktail — capable of covering the spikes of the coronavirus in several places, thus preventing the virus from developing resistance to antibodies using mutations.

The researchers selected eight potent nanobodies and found that several work against Alpha, the UK variant and Delta, as well as several other SARS-CoV-2 variants.

In a previous study, it was found that the nanobodies can sit at room temperature for six weeks and can be fashioned into an mist that can inhaled as an antiviral therapy sent into the lungs — directly where they are most needed for severe COVID-19 patients with respiratory symptoms.