Press release
Tuesday, December 22, 2020
Preliminary results suggest that anti-COVID19 nanobodies may be effective in preventing and diagnosing infections.
Researchers at the National Institutes of Health isolated a set of promising, tiny antibodies, or “nanobodies,” against SARS-CoV-2, which were produced by a blade called Cormac. Preliminary results published in scientific reports suggest that at least one of these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing the SARS-CoV-2 peak proteins. In addition, the nanobody appears to function just as well, either in liquid or aerosol form, suggesting that it may remain effective after inhalation. SARS-CoV-2 is the virus that causes COVID-19.
The study was led by a pair of neurologists, Thomas J. “TJ” Esparza, BS and David L. Brody, MD, Ph.D., who work in a brain imaging lab at the National Institute of Neurological Disorders and Accident. NIH cerebral vascular. (NINDS).
“For years, TJ and I have been testing how to use nanobodies to improve brain imaging. When the pandemic broke out, we thought it was a unique situation in life, completely at hand, and we joined the fight, ”said Dr. Brody, who is also a professor at the University of Uniformed Services for Science. of Health and senior author of the study. We hope that these anti-COVID-19 nanobodies can be extremely effective and versatile in combating the coronavirus pandemic.
A nanobody is a special type of antibody produced naturally by the immune system of camelids, a group of animals that includes camels, llamas and alpacas. On average, these proteins make up about a tenth of the weight of most human antibodies. This is because isolated nanobodies in the laboratory are essentially free floating versions of the arm tips of the heavy chain proteins that form the backbone of a typical human IgG Y-shaped antibody. These tips play a critical role in defending the immune system by recognition of proteins from viruses, bacteria and other invaders, also known as antigens.
Because nanobodies are more stable, less expensive to produce, and easier to design than typical antibodies, a growing body of researchers, including Mr. Esparza and Dr. Brody, have used them for medical research. For example, a few years ago scientists showed that humanized nanobodies can be more effective in treating an autoimmune form of thrombocytopenic purpura, a rare blood disorder, than current therapies.
Since the pandemic broke out, several researchers have produced blade nanobodies against the SARS-CoV-2 protein that may be effective in preventing infections. In the current study, the researchers used a slightly different strategy than others to find nanobodies that could work particularly well.
The SARS-CoV-2 spike protein acts as a key. It does this by opening the door to infections when it binds to a protein called the angiotensin 2 conversion enzyme receptor (ACE2), which is found on the surface of cells, ”said Mr Esparza, who is also an employee of the company. Henry M. Jackson Foundation for the Advancement of Military Medicine and lead author of the study. We developed a method that would isolate nanobodies that block infections by covering the teeth of the protein that binds and unblocks the ACE2 receptor.
To do this, the researchers immunized Cormac five times over 28 days with a purified version of the SARS-CoV-2 protein. After testing hundreds of nanobodies, they found that Cormac produced 13 nanobodies that could be strong candidates.
Initial experiments suggested that a candidate, named NIH-CoVnb-112, could work very well. Test tube studies have shown that this nanobody bound to the ACE2 receptor is 2 to 10 times stronger than nanobodies produced by other laboratories. Other experiments suggested that the NIH nanobody adhered directly to the ACE2 receptor binding portion of the spike protein.
Then, the team showed that the NIH-CoVnB-112 nanobody could be effective in preventing coronavirus infections. To mimic the SARS-CoV-2 virus, the researchers genetically mutated a harmless pseudovirus so that they could use the spike protein to infect cells that have human ACE2 receptors. The researchers found that relatively low levels of NIH-CoVnb-112 nanobodies prevented the pseudovirus from infecting these cells in Petri dishes.
Importantly, the researchers showed that the nanobody was just as effective in preventing infections in petri dishes when sprayed with the type of nebulizer or inhaler, often used to help treat asthma patients.
One of the interesting things about nanobodies is that, unlike most common antibodies, they can be aerosolized and inhaled to cover the lungs and airways, Dr. Brody said.
The team applied for a patent for the NIH-CoVnB-112 nanobody.
“Although we have much more work to do, these results are a promising first step,” said Mr Esparza. With the support of NIH we are moving quickly to test whether these nanobodies could be safe and effective preventive treatments for COVID-19. Collaborators are also working to find out if they could be used for cheap and accurate tests. “
This study was supported by NIH intramural research programs from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Environmental Health Sciences (NIEHS); Dr. Brody is an employee of Uniformed Services University of the Health Sciences. The views expressed herein do not constitute those of the Department of Defense.
NINDS is the largest national funder of research on the brain and nervous system. The mission of NINDS is to seek basic knowledge about the brain and nervous system and to use this knowledge to reduce the burden of neurological diseases.
About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit https://www.niehs.nih.gov or subscribe to a news list.
About the National Institutes of Health (NIH):
NIH, the national medical research agency, includes 27 institutes and centers and is a component of the US Department of Health and Human Services. NIH is the first federal agency to conduct and support basic, clinical, and translational medical research and investigate the causes, treatments, and cures of both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Article
Esparza, TJ et al., High affinity nanocorpions block the interaction of the SARS-CoV-2 receptor binding domain with the human angiotensin converting enzyme. Scientific reports, 22 December 2020 DOI: 10.1038 / s41598-020-79036-0.