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Science: The new research found the Achilles heel of the coronavirus
Science: The new research found the Achilles heel of the coronavirus. According to a new paper published online on the 13th in the journal Science, a research team from the Swiss Polytechnic University of Zurich, the University of Berne, the University of Lausanne and the University of Cork from Ireland found the The “fatal weakness” of the coronavirus, including the new coronavirus.
The study successfully revealed for the first time the interaction between the viral genome and the ribosome in the “frameshift” process, and found that the virus has “fine control” over the ribosome “frameshift” process, which is expected to promote the inhibition of the virus by interfering with the “frameshift” process Development of replicated drugs.
The virus needs to infect cells in order to replicate itself, then infect other cells, and further infect other individuals. An important step in the life cycle of a virus is to use the cell’s own ribosomes to synthesize the proteins it needs. According to this “plan”, ribosomes will synthesize new viral proteins according to the instructions in the viral RNA genome.
For healthy cells that are not infected with the virus, ribosomes move along the RNA “step by step”, reading three RNA letters at a time. This three-letter code defines the corresponding amino acid attached to the growing protein. Sometimes, the ribosome does not follow the usual steps of reading three letters, but will miss one or two RNA letters. This misalignment of the ribosome is called a “frameshift”, which causes the ribosome to read the genetic code incorrectly.
The occurrence of “frameshift” in healthy cells can cause cellular protein dysfunction. However, some viruses, such as coronavirus and HIV, rely on “frameshifting” to regulate the levels of viral proteins. For example, the new coronavirus relies heavily on the “frameshift” caused by its RNA folding to synthesize proteins.
Therefore, because “frameshift” is essential for viruses, any compound that inhibits “frameshift” by targeting RNA folding may be used as a drug for the treatment of infection. However, so far there is no information on how viral RNA interacts with ribosomes to promote frameshift.
Through complex biochemical experiments, the researchers managed to capture ribosomes at the “frameshift” site of the new coronavirus RNA genome. Then, through cryo-electron microscopy studies, it was found that the viral RNA will form a pseudoknot structure, staying at the entrance of the ribosomal mRNA channel, creating tension in the mRNA and promoting the “frameshift”, and the new viral polyprotein and ribosomal channel Form an obvious interaction. In other words, the interaction between the pseudoknot and the ribosome causes the “frameshift” to occur.
Previous studies have reported that fluoroquinolones can inhibit the “frameshift” efficiency of new coronaviruses and other coronaviruses. This study shows that a molecule called merafloxacin is a compound that better inhibits the “frameshift” process. It can reduce the titer of the new coronavirus by 3-4 orders of magnitude and is not toxic to cells.
(source:internet, reference only)