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The Llama nano could become a powerful new weapon against COVID-19



Yufei Xiang holds 3D printed models of nanobodies

Lead author Yufei Xiang holds a 3D printed model of nanobodies (purple) on top of the mutant protein SARS-CoV-2 (gray). Credit: UPMC

Described by researchers at the University of Pittsburgh Medical School, in the journal Science, a new method for small but extremely powerful extraction SARS-CoV-2 antibody fragments from llamas, which can be formed as inhaled treatments with preventive and therapeutic capabilities COVID-19.

These special antibodies from llama, called “nanocomposites”, are much smaller than human antibodies and are many times more effective in inactivating the SARS-CoV-2 virus. They are also much more stable.

“Nature is our best inventor,” said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. “The technology we developed investigating SARS-CoV-2 deactivated nanoparticles on an unprecedented scale allowed us to quickly detect thousands of nanoparticles with neutral affinity and specificity. song. “

To create these nano bodies, Shi sought out a black llama named Wally – who resembles and therefore shares the nickname with Shi’s black Labrador.


Dr. Yi Shi, senior author of the article published in Science, explains how “nanoparticles” can become powerful new weapons against the COVID-19 pandemic. Credit: UPMC

Shi and his colleagues immunized llama with a mutated SARS-CoV-2 protein and after about two months, the animal’s immune system produced mature nanocomposites that resist the virus.

Using the mass spectrometry technique Shi perfected over the past three years, lead author Yufei Xiang, Shi’s lab research assistant, identified the nanocrystals in Wally’s blood that most strongly bound to SARS-CoV-2.

Then, with the help of Pitt’s Center for Vaccine Research (CVR), the scientists exposed their nano-bodies to live SARS-CoV-2 virus and discovered that only one was needed. A fraction of a nanogram can neutralize enough virus to keep a million cells from becoming infected.

Wally the Llama

Wally the Llama. Image Providers: Sonya Paske, Capralogics Ltd.

These nano bodies represent some of the most effective therapeutic antibody candidates for SARS-CoV-2, hundreds to thousands of times more effective than other nano llama bodies detected through The same phage display method has been used for decades to look for human monoclonal antibodies.

Shi’s nanoparticles could sit at room temperature for six weeks and tolerate inhalable mist to deliver antiviral therapy directly into the lungs where they are most needed. Because SARS-CoV-2 is a respiratory virus, nanosomes can find and attach to it in the respiratory system, before it has a chance to cause injury.

In contrast, traditional SARS-CoV-2 antibodies, which require intravenous administration, dilute the product all over the body, require much larger doses, and cost patients and insurers around $ 100,000 per course. treatment.

“Nanosomes can be much lower priced,” said Shi. “They are ideal for addressing the urgency and scale of the current crisis.”

In collaboration with Dr. Cheng Zhang at Pitt and Dr. Dina Schneidman-Duhovny at the Hebrew University of Jerusalem, the team discovered that their nanobjects use a variety of mechanisms to suppress SARS-CoV-2. infection. This causes the nano-bodies to be ripe for biotechnology. For example, nano-bodies that bind to different regions on the SARS-CoV-2 virus can be linked together, like a Swiss army knife, in the case of a viral mutation and becomes resistant.

“As a virologist, it is hard to believe how exploiting the quirks of llama antibody production can be converted into the production of a potent vinoweapon against isolated strains of SARS-CoV-2 study, ”said study co-author and CVR Director Paul Duprex, Ph.D.

Reference: “Multi-purpose and multivalent nanomaterials that effectively neutralize SARS-CoV-2” by Yufei Xiang, Sham Nambulli, Zhengyun Xiao, Heng Liu, Zhe Sang, W. Paul Duprex, Dina Schneidman -Duhovny, Cheng Zhang and Yi Shi, November 5, 2020, Science.
DOI: 10.1126 / science.abe4747

Other authors in the study included Sham Nambulli, Ph.D., Zhengyun Xiao, Heng Liu, Ph.D. and Zhe Sang, all of which belong to Pitt.

Funding for this study was provided by the National Institutes of Health (sponsored R35GM137905 and R35GM128641), the University of Pittsburgh Institute of Clinical Science and Translation, Pitt Vaccine Research Center, and the DSF Charity.




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