IMAGE: NIH scientists showed that anti-COVID-19 nanobodies from llama could be an effective tool in the battle against the COVID-19 virus. view more
Credit: Courtesy of Brody lab NIH / NINDS.
Researchers at the National Institutes of Health have unveiled a set of promising, tiny antibodies, or “nanobodies,” against a llama-derived SARS-CoV-2 named 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 capturing SARS-CoV-2 spike proteins. In addition, the nanobody appeared to function equally well 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 neuroscientists, Thomas J. “TJ” Esparza, BS, and David L. Brody, MD, Ph.D., who work in a brain imaging laboratory at the National Institute of Neurological Disorders and NIH Stroke. (NINDS).
“For years TJ and I had been experimenting with how to use nanobodies to improve brain imaging. When the pandemic broke out, we thought it was a once-in-a-lifetime situation. This was once in a lifetime and we got into the fight, “said Dr. Brody, who is also a professor at the University of Apparel Services for Health Sciences and senior author of the study. “We hope that these anti-COVID-19 nanobodies could be very effective and multifunctional in fighting the coronavirus pandemic.”
A nanobody is a special type of antibody that is naturally produced by the immune systems of camelids, a group of animals that include camels, llamas, and alpacas. On average, these proteins are around the tenth weight of most human antibodies. This is because isolated nanobodies in the laboratory are largely free versions of heavy-chain protein arm molecules, which are the backbone of a normal human Y-shaped IgG antibody. The recommendations play a crucial role. that in protecting the immune system by recognizing proteins on viruses, bacteria, and other invaders, also known as antigens.
Because nanobodies are more stable, cheaper to produce, and easier to invent than conventional antibodies, a growing group of researchers, including Mr. Esparza and Drs. Brody, has been using them for medical research. For example, a few years ago scientists showed that human nanobodies may be more effective at treating a self-defense form of thrombotic thrombocytopenic purpura, a rare blood disorder, than conventional therapies.
Since the outbreak of the pandemic, several researchers have developed llama nanobodies against SARS-CoV-2 spike proteins that may be effective in preventing disease. In the current study, the researchers used a slightly different strategy than the others to find nanobodies that could work particularly well.
“The spike protein SARS-CoV-2 acts as a key. It does this by opening the door to disease when it binds to a protein called the angiotensin receptor that converts enzyme 2 (ACE2), which is found on the surface of some cells, “said Esparza, lead author of the study. “We developed a method that would separate nanobodies that prevent infections by covering the teeth of the spike protein that binds to it and releases the ACE2 receptor.”
To do this, the researchers vaccinated Cormac five times over 28 days with a pure version of SARS-CoV-2 spike protein. After testing hundreds of nanobodies they discovered that Cormac was making 13 nanobodies that could be strong candidates.
Initial tests suggested that a single candidate, called NIH-CoVnb-112, may work well. Test tube studies showed that this nanobody attached to the ACE2 receptor was 2 to 10 times stronger than nanobodies produced by other laboratories. Other experiments suggested that the NIH nanobody would directly bind to the ACE2 receptor binding component of the spike protein.
The team then demonstrated that the NIH-CoVnB-112 nanobody could be effective in preventing coronavirus infections. To report the SARS-CoV-2 virus, the researchers genetically modified a harmless “pseudovirus” to use the spike protein to capture cells containing human ACE2 receptors. The researchers found that relatively low levels of NIH-CoVnb-112 nanobodies prevented the pseudovirus from taking up these cells in petri vessels.
Importantly, the researchers showed that the nanobody was just as effective in preventing infections in petri dishes when sprayed through the nebulizer, or inhaler, type often used. to treat patients with asthma.
“One of the interesting things about nanobodies is that, unlike most regular antibodies, they can be aerosolized and inhaled to coat the lungs and airways,” he said. and Dr. Brody.
The team has applied for a patent on the NIH-CoVnB-112 nanobody.
“While there is much more work ahead, these results represent a promising first step,” said Mr Esparza. “With support from the NIH we are rapidly moving forward to test the potential of the nanobodies. that are safe and effective protective therapies for COVID-19. Colleagues are also working to see if they can be used for a free and error-free test. “
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Article:
Esparza, TJ et al., High affinity nanobodies inhibit SARS? CoV? 2 spike binding domain interactions with human angiotensin converting enzyme. Scientific Reports, 22 December 2020
DOI: 10.1038 / s41598-020-79036-0.
This study was supported by the NIH Intramural Research Programs at the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Environmental Health Sciences (NIEHS); Dr. Brody is an employee of the University of Health Sciences Uniform Services. The views expressed herein do not necessarily reflect the views of the Department of Defense.
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