Tiny, robust immune particles derived from the blood of a llama - a domesticated South American camelid - could provide strong protection against every Covid-19 variant, including Omicron, and 18 similar viruses including SARS-CoV-2 and SARS-CoV-1, responsible for the 2003 SARS outbreak, according to a study.
In a paper published in Cell Reports, the team from Mount Sinai Hospital suggests that these "super-immunity" molecules, known as nanobodies, could be precursors to a fast-acting, inhalable antiviral treatment or spray that could potentially be stockpiled and used globally against the evolving pandemic and future viruses.
Compared to the rest of the animal kingdom, llamas, camels, and alpacas have unique immune systems: they produce antibodies with a single polypeptide chain instead of two. This construct results in antibodies that are roughly one-tenth the size of normal ones, are exceptionally stable, and can firmly bind to disease targets.
Because of these unique properties, researchers can readily link multiple nanobodies like a daisy chain, so if a virus attempts to escape by mutating, another nanobody is ready to keep it in check.
"Because of their small size and broad neutralizing activities, these camelid nanobodies are likely to be effective against future variants and outbreaks of SARS-like viruses," said lead author Yi Shi, Associate Professor at the Icahn School of Medicine at Mount Sinai.
"Their superior stability, low production costs, and the ability to protect both the upper and lower respiratory tracts against infection mean they could provide a critical therapeutic to complement vaccines and monoclonal antibody drugs if and when a new Covid-19 variant or SARS-CoV-3 emerges," Shi added.
In their study, Shi's team immunized the llama, named "Wally," with the SARS-CoV-2 receptor-binding domain (RBD), the short fragment or spike of the virus that latches onto the protein on the surface of human cells to gain entry and spread infection.
They found that repeated immunization with the RBD resulted in Wally producing nanobodies that recognized not just SARS-CoV-2, the virus that causes Covid-19, but a vast array of other coronaviruses -- conferring what researchers referred to as "super-immunity."
From this discovery, the team isolated and validated a large repertoire of highly potent antiviral nanobodies effective against a broad spectrum of SARS-like viruses.
"We learned that the tiny size of these nanobodies gives them a crucial advantage against a rapidly mutating virus," explains co-author Ian Wilson, Professor of Structural Biology at Scripps Research in California.
"Specifically, it allows them to penetrate more of the recesses, nooks, and crannies of the virus surface, and thus bind to multiple regions to prevent the virus from escaping and mutating," Wilson said.
From this structural information, the team designed an ultrapotent nanobody that can simultaneously bind to two regions on the RBD of SARS-like viruses to prevent mutational escape.
The resulting molecule (PiN-31) is extremely stable and, in its aerosolized form, can be used as an inhaled treatment or spray, which the same team showed in previous work can be effective against SARS-CoV-2.
"While more research is needed, we believe that the broad protection, ultrapotent nanobodies we were able to isolate in the lab can be harnessed for use in humans," said Shi. (AS/NewsGram)
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