"In terms of using human cell resources to synthesize Viral protein, COVID-19 did not evolve in the direction of highest efficiency and optimal mechanism, but showed an evolutionary trend of 'de optimization'." On June 25, Lu Jian, a professor of Peking University, introduced in an interview with Science and Technology Daily that this conclusion came from his cooperative research with Qian Zhaohui, a research group of the Chinese Academy of Medical Sciences, They analyzed more than 9 million high-quality COVID-19 sequencing sequences. "There is a process of mutual game between COVID-19 and human cells in resource competition, and the current mutant strains show a trend of 'moderate' use of human cell resources." Lu Jian introduced that the relevant research results have been published in the international journal Advanced Science a few days ago. What inhibits the replication efficiency of Omicron? The survival essence of the virus is to use the protein synthesis machine in the host cell to assemble more virus offspring. According to common sense, the evolution of viruses should make assembly work more efficient and smooth. "After analyzing the sequencing sequence of more than 9 million COVID-19 viruses, we observed a trend of 'de optimization' of codon use." Lu Jian explained that "de optimization" is the change of virus sequence, which makes it more and more difficult to synthesize proteins in human cells, as if he dug more holes for himself, limiting the speed of Viral protein synthesis. Why are the assembled proteins all the same, but the speed is getting slower and slower? This is because species have preferences in codon usage, and when translating the same protein, the efficiency of different codons is different. "Lu Jian said, almost every amino acid has more than one codon, just like using different" synonyms "to express a meaning. The more" synonyms "human cells prefer to use, the faster the protein synthesis speed is, and vice versa, the optimization is needed. The team analyzed the sequence of BA. 2.12.1, BA. 4-5, XBB. 1.5 and other branches in Omicron, and found that the optimized proportion of Omicron was only about 60%, far lower than most human genes. Therefore, when using human Ribosome to synthesize proteins, the Omicron family could not "fully open up", which may inhibit the replication and transmission efficiency of the virus. The team also evaluated 70 pairs of COVID-19 sequences in vitro through the experimental method of double luciferase. The results showed that COVID-19 preferred codons tended to enhance the efficiency of protein expression, while non preferred codons reduced the efficiency of protein expression, further confirming the impact of sequences on translation efficiency. The new findings help to optimize the COVID-19 vaccine. In the past, it was thought that the synonymous mutation of gene sequence would not affect the cell function and the adaptability of organisms because it did not change the protein sequence. However, this study revealed for the first time the influence of synonymous mutations of COVID-19 on the efficiency of viral protein expression on a large scale, and further proved that synonymous mutations can affect many biological processes, including the structure and stability of mRNA (Messenger RNA), the efficiency of protein translation and Protein folding. So why does COVID-19 have such a change? There are specialized protein families in human cells that can mediate base changes in the gene sequences of foreign viruses, and we believe that it is precisely this editing system (APOB) in the human body