Attempt to prevent cell infection by creating a 'bait' for the receptor bound by the new coronavirus
Infection with the
Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2 | Science
https://science.sciencemag.org/content/early/2020/08/03/science.abc0870
Decoys could trick COVID-19, keep humans safe from infection | Live Science
https://www.livescience.com/decoy-ace2-receptor-for-covid19.html
SARS-CoV-2 has protrusions called 'spike proteins' on the surface of the virus, and this spike protein binds to the receptor called angiotensin converting enzyme 2 (ACE2) in human cells Infect cells. It is known that the ACE2 receptor targeted by SARS-CoV-2 when it infects humans is abundant in respiratory organs such as the nasal cavity and lungs, and the intestine.
Research results that the new coronavirus identified human somatic cells to be targeted at infection-GIGAZINE
A team of researchers from the University of Illinois , the U.S. Army Institute of Infectious Diseases , and medical startup Orthogonal Biologics have created a 'bait' that mimics the ACE2 receptor, and is trying to prevent SARS-CoV-2 infection. I am studying about. In a new paper published by the research team, SARS-CoV-2 bound to the bait of the ACE2 receptor developed by the research team on the experimental dish, and SARS-CoV-2 once bound to the bait is a primate cell. It has been reported that it did not combine with.
If it is confirmed that the decoy of the ACE2 receptor functions in the human body similarly to the cells cultured in the experimental dish, the decoy is used to treat the novel coronavirus infection (COVID-19) and SARS. -It may lead to the development of preventive medicine for CoV-2 infection. Attempts to develop a bait receptor as an antiviral drug have been made for a long time, and in a 2008 report , a bait for CD4 expressed in immune system cells was produced as a therapeutic agent for human immunodeficiency virus (HIV) , and it was identified as HIV. There are reports of attempts to combine them.
However, while the CD4 decoy bound effectively to HIV strains grown in the laboratory, it did not bind well to HIV strains isolated from actual patients. In addition, decoy receptors did not function well in experiments targeting rhinovirus , foot- and- mouth disease virus , hepatitis A virus , and SARS coronavirus (SARS-CoV) . At the time of writing, there are some decoy receptors approved for the treatment of immune and inflammatory diseases, but no decoy receptor has been approved as an antiviral drug.
At the time of article writing, the ACE2 receptor decoy is still in the early stages of research, and if approved as a treatment for SARS-CoV-2, it will be the first decoy receptor approved as an antiviral agent. 'If this succeeds, it will be something new,' said Erik Procko, associate professor of biochemistry at the University of Illinois.
Procko points out that there are two important challenges for decoy receptors to be approved as antivirals. The first challenge is that the decoy receptor should not interfere with the functioning of the natural receptor. Since the ACE2 receptor has a function of controlling blood volume and blood pressure in the body, it is necessary to confirm the safety of the decoy receptor in animal experiments and clinical trials. SARS-CoV-2 binds to the ACE2 receptor and interferes with its role, so the ACE2 receptor decoy may protect natural receptors from SARS-CoV-2 and potentially maintain its function. I have it.
The second point is that the decoy receptor must have a high affinity for the target virus. The research team tested thousands of combinations of amino acids and proteins in developing the ACE2 receptor decoy and found that the decoy receptor called ' sACE2.v2.4 ' was the most likely to bind to SARS-CoV-2. I have found Although sACE2.v2.4 has a slightly different protein sequence from the natural ACE2 receptor, it seems that the difference in the protein sequences of both is less than 1% of the whole.
The bait receptor is likely to be delivered to the body by injection or inhalation of mist in the form of being mixed with multiple antibodies that bind to SARS-CoV-2 in different forms. Because SARS-CoV-2 is repeatedly mutated, certain antibodies may not work against SARS-CoV-2. On the other hand, the researcher points out that the receptors used to enter cells are unlikely to change due to mutations, and that the decoy receptors that mimic the ACE2 receptor will be more reliable in the long run.
A medical company called Apeiron Biologics is also looking for an attempt to use the ACE2 receptor decoy to prevent SARS-CoV-2 infection. The decoy receptor developed by Aperion Biologics is closer to the native ACE2 receptor than the one developed by Procko's research team and has not been engineered to bind to SARS-CoV-2 more easily, but in humans. Research results have been reported that there are no serious side effects even after administration (PDF file) .
While the decoy receptors developed by Procko's research team and those developed by Aperion Biologics are different, the initial results reported by Aperion Biologics suggest that the ACE2 receptor decoys may hope to be safe for humans. Argues Procko. It seems that the research team has already started animal experiments using SARS-CoV-2 infected mice, and toxicity has not been observed yet.
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