As the fight against COVID-19 continues, scientists have turned to an unlikely source for a potentially effective treatment: tiny antibodies naturally generated by llamas.
While the world has welcomed the news of multiple vaccines against COVID-19, the search for effective treatments for those who contract the virus is ongoing. Now scientists are looking to what might seem to be an unlikely source: the South American llama.
Researchers are using the ultrabright X-rays of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory, to help turn naturally generated llama antibodies into potentially effective therapies against SARS-CoV-2, the virus that causes COVID-19. Antibodies are the immune system’s natural defense against infection, and when extracted from blood, they can be used to design treatments and vaccines.
“Llamas generate these nanobodies naturally in high yields, and they fit into the pockets on the surface of proteins that larger-size antibodies can’t access.” — Jason McLellan, The University of Texas at Austin.
“We have received more than 50 llama antibodies with several proteins of SARS-CoV-2,” said Andrzej Joachimiak, director of the Structural Biology Center (SBC) at the APS and co-director of the Center for Structural Genomics of Infectious Diseases. (Researchers at the APS do not work with the live virus, but with crystals grown from simulated proteins.) These antibodies are part of ongoing collaborations with several partners, including researchers at the National Institutes of Health (NIH) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Joachimiak said, and will be analyzed using the APS to see if they combat the virus’s infectivity.
While it may seem surprising that scientists are turning to llamas, there’s a very good reason for it.
Llamas belong to a group of mammals called camelids, a group that also includes camels and alpacas. Thanks to a quirk of nature, camelids produce a unique type of antibody against disease. These antibodies, often referred to as nanobodies, are about half the size of the antibodies produced by humans. They’re also remarkably stable and easy for scientists to manipulate.
This genetic quirk, which causes camelids such as llamas to produce these smaller antibodies with single protein chains, was discovered by accident in the late 1980s by scientists in Belgium. Since then, scientists have worked with camelid nanobodies to create treatments against several diseases with great success. Their small size allows them to bind to areas of viral proteins that larger antibodies cannot fit into, blocking those proteins from connecting with cells.
“Llamas generate these nanobodies naturally in high yields, and they fit into the pockets on the surface of proteins that larger-size antibodies can’t access,” said Jason McLellan, an associate professor at The University of Texas at Austin.
McLellan has years of experience working with camelid nanobodies. He and his graduate student Daniel Wrapp, along with Xavier Saelens’ group in Belgium, have isolated nanobodies that have proven effective against respiratory syncytial virus (RSV) and two coronaviruses: severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
When the genetic sequence of SARS-CoV-2 was released in January of 2020, McLellan, Wrapp and Saelens worked quickly to test whether any of the antibodies that they had previously isolated against the original SARS-CoV (taken from a Belgian llama named Winter) could also bind and neutralize SARS-CoV-2. They discovered that one of these nanobodies, which they had characterized using the SBC beamlines at the APS, might be effective against SARS-CoV-2. McLellan said this nanobody — called VHH72 — is now under development as a treatment for COVID-19. He and Wrapp received a 2020 Golden Goose Award for this research.Original Source