新冠病毒,细胞诱饵 z-bo 2020-10-30 340

　　In the past few months, scientists have done everything they can to develop treatments against COVID-19, from stem cells and synthetic antibodies to ordinary over-the-counter drugs and tried-and-tested steroids. Some people even try to lure SARS-CoV-2 coronavirus away from human cells by using molecular baits. But few people try to use fake human cells to distract the new coronavirus. Now, in a new study, researchers from China's Fudan University, Wuhan University, Jinan University, and the National Institutes of Health (NIH) report that genetically modified cells can neutralize the coronavirus in vitro. They imagined that such cell decoys might be used to fight infections.

　　Bengt Fadeel, a molecular toxicologist at the Karolinska Institute in Sweden (who did not participate in this study) said, “This is a very elegant study. As long as you know the receptors of a particular virus, in principle, you can use this Way to stop any virus."

　　When the SARS-CoV-2 virus began to spread globally at the beginning of this year, Chen shifted from developing nanotechnology for the diagnosis and treatment of cancer to researching SARS-CoV-2. He has seen reports of using decoy receptors to deceive HIV and other pathogens, so he is curious whether this emerging technology can work against SARS-CoV-2.

　　To find out, these researchers fused membranes from human monocyte THP-1 (a cell line derived from leukemia) with membranes from human embryonic kidney cells that overexpress the ACE2 receptor. SARS-CoV -2 will grab this receptor to invade the cell. Chen said they hope that if these fusion vesicles are injected into the body, the virus will ignore human cells that have not been genetically modified and target cell decoys (that is, genetically modified cells). According to Chen, once attached to the ACE2 of genetically modified cells, the virus is absorbed and neutralized.

　　By embedding monocyte membranes with cytokine receptors into these engineered vesicles, these cell decoys can bind to inflammatory cytokines such as IL-6 to prevent their accumulation and cause a cytokine storm, which is considered to cause more serious COVID -19 excessive immune response.

　　The idea of using bait to thwart SARS-CoV-2 infection is not new. A team of scientists used genetically modified, free-floating ACE2 receptors to create a bait that binds the virus particularly well. This bait can "significantly block the early stages of SARS-CoV-2 infection" and is now in phase 2 clinical trials conducted by Apeiron Biologics. In a preprint article published in July this year, Gaurav Sahay, a pharmacologist at Oregon State University in the United States, described a method of using lipid nanoparticles to deliver engineered mRNA encoding ACE2 to the liver of mice, thereby making ACE2 decoy Can be expressed and secreted into the blood. He found that this method successfully increased ACE2 decoys in the body, and they inhibited a genetically modified, non-pathogenic SARS-CoV-2 in vitro.

　　Chen's new expansion of this concept is to couple the bait to the cytokine receptor. Sahay said, "The combination of [ACE2 and cytokine receptor] in this vesicle structure is a new thing. This is a very exciting new development."

　　These researchers tested their nanodecoys (nanodecoy, the aforementioned cell decoy) by culturing SARS-CoV (which caused the SARS epidemic in 2003) and SARS-CoV-2 (which caused COVID-19) in human and monkey cells It turned out that these nano-baits can significantly inhibit viral infections regardless of the cell or virus type.

　　In order to test whether these decoys can work outside the petri dish, these researchers inhaled the irritant lipopolysaccharide in mice, which induced acute lung inflammation in the mice. After four hours, the mice inhaled the nanobait, and eight hours later, they collected the fluid from their lungs. They found that, compared with mice that did not receive these baits, these baits successfully eliminated cytokines in mice that received them.

　　Chen said, "This research is quite straightforward. It is surprising that such a simple method can neutralize the virus at least at the cellular level and neutralize cytokines within a few hours in the body. For COVID-19 In terms of fast response is essential, and these nano decoys can do just that."

　　Although these results indicate that these baits can neutralize cytokines in the lungs of mice, their ability to block SARS-CoV-2 infection has not been tested in mice. Chen pointed out that there is currently a lack of transgenic mice carrying the human ACE2 gene, which will be necessary for such experiments.

　　Fadeel said that the mice that received these nanobaits did not have any adverse reactions to the treatment, which was encouraging, but he said he wanted to know whether this could also be true in humans, especially because of these genetically modified ones. The cells use materials from human cancer cells. He said, "I would be cautious about administering a small amount of cancer cells, especially into the lungs."

　　Sahay also pointed out that the cell membranes in the lungs, arteries, heart, kidneys and intestines produce ACE2 for a reason-it can cut angiotensin, a protein that raises blood pressure. He doubted whether these decoys would impair the body's ability to regulate blood pressure, because angiotensin may bind to these decoys.

　　None of these researchers currently plan to test these decoys on humans. Chen said, "This is a very simple method --- almost too simple. This is the charm of this research."