Scientists develop 'highly potent' stable nanobody cocktail that neutralises SARS-CoV-2

Researchers from Max Planck Institute (MPI) for Biophysical Chemistry in Germany have developed a cocktail that is able to block ACE2 engagement with receptor-binding domain (RBD) of coronavirus, potently neutralizing SARS-CoV-2’s mutations present in UK variant and has also appeared convergently in the Brazil P. 1 and South Africa B. 1.351 variant. The nanobody cocktail was found to be drastically reducing viral load, and effectively neutralizing coronavirus’ dangerous new variants. The so-called highly potent and stable nanobodies bind and neutralize the virus up to 1,000 times better than previously developed mini-antibodies and were developed from the blood of alpacas, according to the study published in both scientific journals PNAS and  The EMBO.

These high-affinity nanobodies were found to be very cost-effective and showed longtime stability and resistance to extreme heat. They are a unique combination that makes them promising agents to treat COVID-19, scientists said in the study, adding that they can be produced in large quantities. Nanobody cocktail effectively immunized the coronavirus spike and receptor-binding domains (RBD) that disrupted its engagement with the human receptor ACE2, as a result, killing the SARS-CoV-2 virus that causes COVID-19. Furthermore, the epitope mapping, X-ray crystallography, and cryo-electron microscopy procedures found that these cocktails contained two neutralizing nanobodies bound simultaneously that neutralized both aggressive SARS-CoV-2 and the N501Y D614G, mutations common to all its variants. This mixture reduced viral loads by up to 40-fold in mice. 

“Alpacas, llamas, and camels have evolved one of the smallest naturally occurring antigen recognition domains called nanobodies,” the study revealed. It added, nanobodies display strong binding affinities to target proteins, like that of coronavirus, and are “highly suited to be developed as a potential bio-inhaled therapies against respiratory diseases.” 

Limited research was done previously on efficacy of nanobodies

The study purports that very few researchers have examined the in vivo efficacy of nanobodies for the prevention and treatment of COVID-19. "For the first time, they combine extreme stability and outstanding efficacy against the virus and its Alpha, Beta, Gamma, and Delta mutants," said Dirk Gorlich, director at the MPI for Biophysical Chemistry. Separately,  a professor and director of the UMG's Institute of Molecular Oncology, Matthias Dobbelstein stated that these nanobodies can withstand temperatures of up to 95 degrees Celsius without losing their function or forming aggregates. 

"For one thing, this tells us that they might remain active in the body long enough to be effective. For another, heat-resistant nanobodies are easier to produce, process, and store," Dobbelstein said. He added, that they bind extremely effectively to the mutated receptor-binding domains of the Alpha, Beta, Gamma, and Delta strains.