[ad_1]
The search for an effective treatment for COVID-19 has led a team of investigators to find an unlikely ally for their job: a llama named Winter. The team, from the University of Texas at Austin, the National Institutes of Health and the University of Ghent in Belgium, report their findings on a possible route for a coronavirus treatment involving flames on May 5 in the journal Cell. The document is currently available online as a “pre-test”, which means it is peer reviewed but is in the process of final formatting.
The researchers linked two copies of a special type of antibody produced by flames to create a new antibody that binds tightly to a key protein in the coronavirus that causes COVID-19. This protein, called the spike protein, allows the virus to break down in host cells. Initial tests indicate that the antibody blocks viruses that show that this spike protein infects cells in culture.
“This is one of the first known antibodies to neutralize SARS-CoV-2,” said Jason McLellan, associate professor of molecular biosciences at UT Austin and senior co-author, referring to the virus that causes COVID-19.
The team is now preparing to conduct preclinical studies on animals such as hamsters or non-human primates, in hopes of conducting the next tests on humans. The goal is to develop a treatment that will help people soon after infection with the virus.
Vaccines should be given one to two months before infection to provide protection. With antibody therapies, you are giving the protective antibodies directly to someone, and therefore, immediately after treatment, they must protect themselves. Antibodies could also be used to treat someone who is already sick to decrease the severity of the disease. “
Jason McLellan, associate professor of molecular biosciences at UT Austin
This would be especially useful for vulnerable groups such as the elderly, who have a modest response to vaccines, which means that their protection may be incomplete. Health workers and others at increased risk of exposure to the virus can also benefit from immediate protection.
When the flame’s immune systems detect foreign invaders like bacteria and viruses, these animals (and other camelids like alpacas) produce two types of antibodies: one that is similar to human antibodies and another that is only a quarter of the size. These smaller ones, called single domain antibodies or nanobodies, can be nebulized and used in an inhaler.
“That makes them potentially really interesting as a drug for a respiratory pathogen because you take it directly to the site of infection,” said Daniel Wrapp, a graduate student in McLellan’s lab and co-author of the article.
Know the winter
Winter, the llama, is 4 years old and still lives on a farm in the Belgian countryside along with approximately 130 other llamas and alpacas. His part in the experiment occurred in 2016 when he was about 9 months old and researchers were studying two previous coronaviruses: SARS-CoV-1 and MERS-CoV. In a process similar to that of humans receiving vaccines to immunize them against a virus, they were injected with stabilized peak proteins from those viruses over the course of approximately six weeks.
The researchers then collected a blood sample and isolated antibodies that bound to each version of the spike protein. One proved to be really promising in stopping a virus that shows SARS-CoV-1 peak proteins from cultured infecting cells.
“That was exciting for me because I had been working on this for years,” said Wrapp. “But there was not a great need for coronavirus treatment at the time. This was just basic research. Now, this may also have some translational implications.”
The team designed the new antibody that looks promising for the treatment of current SARS-CoV-2 by linking two copies of the flame antibody that worked against the previous SARS virus. They demonstrated that the new antibody neutralizes viruses that show SARS-CoV-2 peak proteins in cell cultures. Scientists were able to complete this research and publish it in a leading journal in a matter of weeks thanks to the years of work they had already done on related coronaviruses.
McLellan also led the team that first mapped the SARS-CoV-2 spike protein, a critical step toward a vaccine. (Wrapp also co-authored that document along with other authors on the current topic. Cell article, including Nianshuang Wang of UT Austin, and Kizzmekia S. Corbett and Barney Graham of the National Vaccine Research Center of the National Institute of Allergy and Infectious Diseases.) In addition to Wrapp, the other co-first author of the article is Dorien De Vlieger, a Postdoctoral scientist at The Vlaams Institute for Biotechnology (VIB) at the University of Ghent, and the other lead authors besides McLellan are Bert Schepens and Xavier Saelens, both at VIB.
This work was supported by the National Institute of Allergy and Infectious Diseases (USA), VIB, The Research Foundation-Flanders (Belgium), Flanders Innovation and Entrepreneurship (Belgium), and the Federal Ministry of Education and Research (Germany).
Background
The first antibodies the team identified in initial tests of SARS-CoV-1 and MERS-CoV included one called VHH-72, which bound strongly to the peak proteins in SARS-CoV-1. By doing so, it prevented a pseudotyped virus, a virus that cannot make people sick and that has been genetically engineered to display copies of the spike protein SARS-CoV-1 on its surface, from infecting cells.
When SARS-CoV-2 emerged and triggered the COVID-19 pandemic, the team wondered if the antibody they discovered for SARS-CoV-1 would also be effective against its viral cousin. They found that it also bound to the SARS-CoV-2 peak protein, albeit weakly. Engineering them to bind more effectively involved pairing two copies of VHH-72, which they later showed neutralizes a pseudotyped virus with sporty spike proteins from SARS-CoV-2. This is the first known antibody that neutralizes both SARS-CoV-1 and SARS-CoV-2.
Four years ago, De Vlieger was developing influenza A antivirals when asked by Bert Schepens and Xavier Saelens if she would be interested in helping to isolate coronavirus antibodies from flames.
“I thought this would be a small side project,” he said. “Now the scientific impact of this project has gotten bigger than I could have hoped for. It’s amazing how unpredictable viruses can be.”
Source:
University of Texas at Austin
[ad_2]
