The Sars-CoV-2 pandemic has been and remains one of the world’s major health problems. A complete understanding of the pathogenesis of Sars-CoV-2 and the molecular mechanisms of infection provides great opportunities to overcome the pandemic. Shedding light on the functions of viruses and host-virus interactions will help develop targeted treatments, vaccines or other preventative measures, the Max Planck Institute wrote in a press release. However, the study of Sars-CoV-2 in the laboratory faces many challenges. One is the increased safety requirements for experiments, the other is the study of different mechanisms during infection, rather than the entire pathogenesis, to better understand these individual processes.
Creation of artificial virions SARS-CoV-2
Researchers from the Max Planck Institute for Medical Research and their colleagues used their expertise in synthetic biology from the bottom up to overcome some of these challenges. For their study, they developed artificial virions of Sars-CoV-2. Virions have a similar structure to natural viruses, but do not contain any genetic information. Therefore, they can be used safely.
“Even more important to us when we build these synthetic virions from scratch is that we can accurately design their composition and structure. This allows us to conduct a very systematic, step-by-step study of the various mechanisms, “said Oscar Staufer, first author, former postdoc at the Max Planck Institute for Medical Research and current postdoc at Oxford University. and characteristics for studying viruses beyond the current application for Sars-CoV-2.
The mechanism of spike protein switching to avoid the immune system?
They first used artificial minimalist virions to study the effects of inflammatory fatty acids on the adhesion protein Sars-CoV-2. Inflammatory fatty acids are released during any inflammation in the body and help facilitate the immune response and healing process. Adhesion protein is crucial for host-virus interaction. On the one hand, the virus uses an adhesion protein to bind to ACE2 receptor host cells. This allows the virus to merge with the host cell and release its genetic information. On the other hand, antibodies produced by the host can bind to the thorn protein, thereby marking the virus as a target for the immune system.
It was previously known that thorn protein has a separate area where inflammatory fatty acids can bind. However, the function of this hardcover pocket was not previously understood. Researchers from the Max Planck Institute for Medical Research and staff at Bristol have now used artificial Sars-CoV-2 virions to study this exact mechanism. They show that when fatty acids bind, the thorn protein changes its structure and “coagulates”. As a result, binding to the host ACE2 receptor is no longer possible, and fewer antibodies can bind to the protein.
Understanding the mechanism of therapy development
Researchers can now begin to understand why this compression mechanism is used by viruses, and determine whether this information can be used to develop therapeutic strategies. “By“ missing ”the thorn protein when binding inflammatory fatty acids the virus becomes less noticeable to the immune system. This can be a mechanism that avoids detection by the host and a strong immune response over a longer period of time and increases the overall effectiveness of the infection, ”says Oscar Staufer. However, scientists are only beginning to determine the function of the coagulation mechanism, but the use of artificial virions will approach the system. “Applying such concepts of synthetic biology to the problem of global impact is truly exciting!” Says Oscar Stauffer.
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