Coincidence?The novel Coronavirus critical sequence was patented by a US pharmaceutical company six years ago

“Novel Coronavirus is manufactured by a US company” has been the subject of intense debate for days. The source of the discussion is an academic paper — researchers conducted a novel Coronavirus sequence study, which led to the discovery of a startling coincidence in a series of clues:A 19-nucleotide sequence in the novel Coronavirus critical position was patented six years ago by Modena, an American pharmaceutical company.Objectively speaking, “the key sequence of novel Coronavirus is patented by a US pharmaceutical company” and “Novel Coronavirus is manufactured by the Company” are two completely different problems.How should we look at these two problems?To get the story straight, let’s follow the paper, review the scholars’ findings, and listen to the experts.In order to find out what is unique about the Novel Coronavirus, many researchers use a comparative method.The novel Coronavirus researchers compared the coronavirus with its closest cousin, a bat coronavirus called RaTG13, showing a 96.3% similarity.If you put two sequences together, you can’t tell the difference by a dozen.But the paper’s researchers did a careful analysis, like playing a game of “find different”, to circle the differences.They were surprised to find that there were few differences of more than three nucleotides in a row. It was like two deserts, with a dune here and a few mounds there, but no skyscrapers.But there was only one surprise, a 12-nucleotide insertion at a key location in the Novel Coronavirus sequence, which was not present in bat coronavirus.A single 12-nucleotide difference stands out like a skyscraper in the middle of a desert.The researchers decided to look it up.At this point, they don’t know what they’re gonna find.Three coincidences in the Novel Coronavirus sequence that researchers consider “rare” what is going on with this abnormal sequence of 12 nucleotide mutations?With this question in mind, researchers conducted two aspects of analysis: functional analysis and sequence analysis.The purpose of functional analysis is to understand what role this sequence plays in the “life course” of the Novel Coronavirus.The researchers identified the protein that translated this sequence.It turns out that the protein it translates happens to be critical.First, the location is critical: it happens to be on the s-protein, the most critical part of the human body in the Novel Coronavirus;Second, it encodes a site that happens to be able to cleft itself with flynase in humans, helping the virus fuse into human cells.Many previous studies have shown that this restriction site is associated with novel coronavirus infection capacity.Sequence analysis is to see if the sequence has been seen elsewhere, and if it has, that might indicate the origin of the sequence.Through the general sequence retrieval method, the researchers found that the complementary matching sequence of this sequence coincidentally appeared in the synthetic sequence patent applied by Modena in 2016, and the matching length was extended from 12 to 19.At the same time, this sequence is relatively rare, present only in the genomes of some bacteria and rarely seen in other species, especially in potential host animals such as bats.To sum up, this sequence leads to at least three coincidences: the sequence happens to appear at the key position of novel Coronavirus and plays a key role in it;The sequence happens to be in modena’s patents (but not anyone else’s);Sequences happen to be absent in most species.The paper was peer-reviewed and published to stimulate discussion, lead author Bala Ambati, a scholar at the University of Oregon in the US, told China Daily recently.The team was more interested in demonstrating experimentally that it was possible to recombine viral sequences with artificially designed ones.With the paper in hand, ScienceDaily spoke exclusively with an expert in molecular virology.Why should we pay attention to the 12 nucleotide length insertions in novel Coronavirus that are different from those in bat coronavirus?”The nucleic acid sequences of the two viruses in this paper differ by more than 1,100 nucleotides, which are evenly distributed among more than 30,000 nucleotides.”The expert explained that, in theory, the longer the continuous variation, the less, and sequence alignment also proves this.In other words, there were the most single mutations, fewer mutations linked to two, fewer mutations linked to three, and almost none more than three.So 12 mutations in a row is really quite unexpected.Just 19 nucleotides are the same, isn’t that tiny compared to the tens or hundreds of millions of genomes?”The 19 nucleotides are continuous, and continuous sameness is highly specific.”Experts explain that the odds of a match drop exponentially with each additional nucleotide in the length of the sequence.With 19 consecutive nucleotides, theoretically there is only a 1 in 19 to the power of 4 nucleotides to find the exact same sequence.It is a rare and incomprehensible coincidence that a specific 19-base synthetic sequence appears at a key site in a viral genome and performs a crucial function.Are these 19 nucleotides the key sequence for the Novel Coronavirus?”Its location is critical, and its functionality is critical.”This, the expert said, is also recognized as an important marker in the scientific community. The novel Coronavirus is directly related to this marker.Is the Novel Coronavirus manufactured by this company?From the patent point of view, the sequence is designed to repair the mismatch in the tumor, because during the tumor expansion process, if the mismatch worsens, the rate and degree of deterioration will be faster, and repairing the mismatch will help the tumor treatment.As to how this sequence is accurately and efficiently inserted into the critical loci of the Novel Coronavirus genome, the current assessment is mostly speculative.Whether it was purely coincidental or intentional requires further investigation and proof.Edited by Zhang Shuang and reviewed by Wang Xiaolong

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