Researchers led by Mount Sinai have shown that tiny, robust immune particles derived from the blood of a flame could provide strong protection against all variants of COVID-19, including Omicron, and 18 similar viruses, including SARS-CoV- 2 and SARS-CoV-1. , who was responsible for the 2003 SARS outbreak.
Study: Superimmunity to pan-sarbecovirus nanocodies. Image credit: Rita_Kochmarjova / Shutterstock
In an article published in Cell Reports on June 28, the team suggests that these “superimmunity” molecules, known as nanocodies, could be precursors to a fast-acting, inhalable antiviral treatment or aerosol that could be stored 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 construction results in antibodies that are approximately one-tenth the size of normal ones, are exceptionally stable, and can be firmly attached to disease targets. Because of these unique properties, researchers can easily link several nanoc bodies such as a chain of daisies, so if one virus tries to escape mutant, another nanocos is prepared to keep it under control.
Due to their small size and extensive neutralizing activities, these camelid nanocodies are likely to be effective against future variants and outbreaks of SARS-like viruses. Their superior stability, low production costs, and ability to protect both the upper and lower respiratory tract against infection mean that they could provide critical therapy to supplement monoclonal antibody vaccines and drugs if and when a new variant of COVID-19 or SARS-CoV-3 emerges “.
Yi Shi, PhD, lead author of the study and associate professor of pharmacological sciences and director of the Center for Protein Engineering and Therapeutics, Icahn School of Medicine in Mount Sinai
As a critical part of his study, Dr. Shi immunized the flame, called “Wally,” with the domain of binding to the SARS-CoV-2 receptor (RBD), the short fragment or spike of the virus that attaches to the protein on the surface of human cells. to enter and spread the infection. They found that repeated immunization with RBD resulted in Wally producing nanoc bodies that recognized not only SARS-CoV-2, the virus that causes COVID-19, but a wide variety of other coronaviruses; conferring what the researchers called “superimmunity.” “From this discovery, the team isolated and validated a broad repertoire of highly potent antiviral nanoc bodies effective against a broad spectrum of SARS – like viruses.
“We’ve learned that the small size of these nanocodies gives them a crucial advantage against a rapidly mutating virus,” explains co-author Ian Wilson, PhD, Hansen Professor of Structural Biology and chair of Scripps Research’s Department of Integrative Structural and Computational Biology. . in La Jolla, California. “Specifically, it allows them to penetrate more into the recesses, nooks and crannies of the virus’s surface and thus bind to various regions to prevent the virus from escaping and mutating.”
Based on this structural information, the team designed an ultra-powerful nanocos that can bind simultaneously to two regions of the SARS-like virus RBD to prevent mutational leakage. The resulting molecule (PiN-31) is extremely stable and, in its aerosolized form, can be used as an inhaled or aerosol treatment, which the same team demonstrated in previous work can be effective against SARS-CoV-2.
“While more research is needed, we believe that the ultra-powerful, broad-spectrum nanoc bodies we were able to isolate in the laboratory can be harnessed for use in humans,” says Dr. Shi, who conducted most of the research at the University of Pittsburgh before. moving his lab to Icahn Mount Sinai. By increasing the attractiveness of this potential form of treatment, these highly versatile antiviral agents can be rapidly produced virtually anywhere from microbes such as E.coli or yeast cells, he adds. In the past, nanobody therapies have been clinically proven to be safe and effective against human diseases, such as a blood clotting disorder and cancer.
“Winning the race against the current pandemic, as well as future viral outbreaks, will depend on the rapid development and equitable distribution of an arsenal of cost-effective and convenient technologies,” Dr. Shi. “We firmly believe that the new, inhalable and extremely potent nanoc bodies we have discovered can meet this global demand, especially in developing countries that are more vulnerable to viruses and the lack of therapies to treat them.”
Source:
Mount Sinai Hospital / Mount Sinai School of Medicine
Magazine reference:
Xiang, Y., et al. (2022) Pan-sarbecovirus nanocorporeal superimmunity. Cell reports. doi.org/10.1016/j.cellrep.2022.111004