A new ally appears in the battle with COVID-19: Wally of Lama | COVID-19

In Science, University of Pittsburgh, PA, researchers at the University of Pittsburgh School of Medicine described a new method for extracting small but highly potent SARS-CoV-2 antibody fragments from llamas. It has the potential to prevent and treat COVID-19.

These special llama antibodies, called “Nanobodies,” are much smaller than human antibodies and are many times more effective in neutralizing the SARS-CoV-2 virus. It’s also much more stable.

“Nature is our best inventor,” said Dr. EC, senior author and assistant professor of cell biology at Pitt. “The technology we have developed has investigated SARS-CoV-2 neutralized Nanobodies on an unprecedented scale, which allows us to quickly discover thousands of Nanobodies with unmatched affinity and specificity. I was able to.”

To generate these Nanobodies, Shi turned to a black llama named Wally. Wally shares his Monica because it resembles Shi’s black Labrador.

Shi et al. Immunized llamas with a portion of the SARS-CoV-2 spike protein, and about two months later, the animal’s immune system produced mature Nanobodies against the virus.

Using mass spectrometry-based technology that Shi has completed over the past three years, lead author Yufei Xiang, a research assistant in Shi’s lab, found that Wally’s blood, which binds most strongly to SARS-CoV-2, Identified Nanobody.

Then, with the help of Pitt’s Vaccine Research Center (CVR), scientists exposed Nanobodies to the live SARS-CoV-2 virus, where only a small portion of the nanogram prevented infection of one million cells. We have found that we can neutralize enough viruses.

These Nanobodies represent some of the most effective therapeutic antibody candidates for SARS-CoV-2 and were discovered by the same phage display method that has been used for decades to search for human monoclonal antibodies. Hundreds to thousands of times more effective than other Ramananobodies.

Shi Nanobodies can be left at room temperature for 6 weeks, allowing them to form into inhalable mist, providing the most needed antiviral therapy directly to the lungs. Because SARS-CoV-2 is a respiratory virus, Nanobodies can find and latch it in the respiratory system before damaging it.

In contrast, conventional SARS-CoV-2 antibodies require IV, which dilutes the product systemically, requiring much higher doses, and patients and insurance companies cost about $ 100,000 per course of treatment. It costs.

“Nanobodies can potentially be much cheaper,” says Shi. “They are ideal for dealing with the urgency and scale of the current crisis.”

The team, in collaboration with Dr. Cheng Zhang of Pitt and Dr. Dina Schneidman-Duhovny of the Hebrew University of Jerusalem, discovered that Nanobodies use a variety of mechanisms to block SARS-CoV-2. infection. This makes Nanobodies suitable for bioengineering. For example, Nanobodies that bind to different regions of the SARS-CoV-2 virus can be linked together like a Swiss Army knife in case part of the virus mutates and becomes drug resistant.

“As a virologist, it’s incredible to see how the quirks of llama antibody production can be transformed into the creation of powerful nanoweapons for clinical isolates of SARS-CoV-2.” Said Dr. Paul Duprex, co-author of the study and CVR director. ..

Additional authors for this study include Dr. Siam Namburi, Dr. Chung Yun, Dr. Heng Liu, and Jae Sang, all of Pitt.

This study was funded by the National Institutes of Health (Grants R35GM137905 and R35GM128641), the University of Pittsburgh Institute for Clinical and Translational Sciences, the Pit Vaccine Research Center, and the DSF Charitable Foundation.