German and American scientists recently published a preprint where they provide new evidence that the coronavirus was artificially created. They cite a 2014 scientific article as an argument, which provides step-by-step instructions for constructing a synthetic coronavirus. The found traces of construction in SARS-CoV-2, in their opinion, are the “fingerprint” of the creator, which is consistently proved in the article. In the circles of Russian geneticists and bioinformatics, after the release of this study, fierce discussions again began. Some consider the article undoubted evidence, others - another fake. What scientists are arguing about - in this material.
New evidence
“We believe that SARS-CoV-2 is an anomaly, most likely a product of synthetic genome assembly rather than natural evolution. We report a high probability that SARS-CoV-2 could have arisen as an infectious clone assembled in vitro, ” says Valentin Bruttel (University Hospital Würzburg - Germany) in a recently published preprint (a scientific article that has not been peer-reviewed ), Alex Washburn (Selva Analytics - a private company from the USA ) and Antonius VanDongen (Duke University, USA).
The published preprint provides new ground for the hypothesis that the coronavirus (Sars-CoV-2) may have escaped from a lab in Wuhan, China, eventually triggering a global pandemic.
Researchers claim to have found in the SARS-CoV-2 genome a kind of “fingerprint” of a genetic engineer, left as a result of targeted manipulations with the virus.
This imprint, according to the authors of the article, is a regularly repeating pattern (a restriction site is a special segment) in the virus genome used by genetic engineers to cut and stitch DNA fragments.
“Scientists who genetically modify RNA viruses (such as SARS-CoV-2) first assemble the genetic makeup from the individual DNA building blocks,” said Valentin Bruttel, quoted by German television channel NTV. One of the commonly used methods suggests that after manipulations in the genome, one can see the remaining "sites of recognition" near the junctions of these building blocks, namely: a characteristic regular pattern.
Bruttel and his colleagues compared the genomes of known artificial viruses and natural viruses with each other. “In natural viruses, the sites of detection (patterns) are distributed in a completely random way,” Bruttel told NTV. “However, in the case of genetically assembled (artificial) viruses, they always appear in a certain, production-driven pattern.”
Scientists drew attention to the fact that this pattern can be found in SARS-CoV-2, but not in closely related viruses.
Their preliminary results showed that the probability of the natural occurrence of this pattern is no more than 1 in 100, and even much lower.
According to Bruttel, this pattern can be compared to a fingerprint on a crime weapon. “We have shown that it is extremely unlikely that such a pattern, which is also found in at least ten other synthetic RNA viruses, appeared in SARS-CoV-2 purely by chance,” NTV quoted him as saying.
"Cookbook"
In addition, the scientists point in their article to a “cookbook” with a recipe, namely the 2014 article “Coronavirus Reverse Genetic Systems: Infectious Clones and Replicons,” which gives instructions on exactly how the coronavirus should be assembled.
According to the authors of the preprint, according to the scheme given in this article, synthetic SARS-CoV-2 was assembled.
Pavel Volchkov, head of the MIPT Laboratory of Genomic Engineering, who in his practice also synthesizes viruses using the reverse genetics method, requested to evaluate the cited article for the popularity of its “recipe”.
“The 2014 article is popular in the circles of scientists who are engaged in the synthesis of viruses using reverse genetics,” says Pavel Volchkov. “If you reverse engineer the coronavirus, you will undoubtedly follow some kind of instruction. First, you need to look at the genetic sequence of the original coronavirus, which we understandably do not have. Then follow the given instructions. Then, after various genetic manipulations, you get a kind of coronavirus. And then an experienced eye looks at the picture shown in the preprint and sees exactly the same restriction sites that must be “inserted according to the instructions” already in the right places in the SARS-CoV-2 genome. From my point of view, this is a “checkmate,” says Pavel Volchkov.
Criticism
However, not all experts agree with the evidence presented. Among the most famous critics is the immunologist Christian Andersen of the Scripps Research Institute (USA). He calls the work "nonsense", stating that the study is "so flawed that it wouldn't even be accepted in molecular biology kindergarten."
German virologist Friedemann Weber, who heads the Institute of Virology at the University of Giessen, claims that it is also possible to genetically manipulate viruses without leaving the traces mentioned by Bruttel and his colleagues - "and this saves time, money, and labor."
A long-time defender of the theory of the natural origin of the coronavirus, a senior researcher at the A. A. Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Russian bioinformatician Alexander Panchin.
According to him, all of these restriction sites in the same places are also found in natural coronaviruses, and some of them were discovered after SARS-CoV-2.
“Previously, the reconstruction of the ancestral genome of SARS-CoV-1, SARS-CoV-2, and related viruses was carried out (Scientific article The comparative recency of the proximal ancestors of SARS-CoV-1 and SARS-CoV-2 ) and this ancestor has all these sites were. Which is inconsistent with the assertion that these sites were allegedly inserted by some kind of genetic engineers,” says Alexander Panchin.
According to the bioinformatician, there are many other problems with the mentioned preprint.
“For example, it is not clear why these restriction sites were chosen, and not others, including those that are more popular with genetic engineers. The most likely answer is that only such sites produced a sensational headline, but in this case, when statistically processing the results, it is necessary to take into account an adjustment for multiple comparisons, which was not done. But even with these sites, even with these authors, you can see natural coronaviruses in the work, which are still more “abnormal” than SARS-CoV-2, ”says Panchin.
The scientist is sure that “This sensation is about nothing, like all previous incorrect evidence of the artificiality of SARS-CoV-2”
Arguments for
Professor of the Department of Genomics and Bioinformatics of the Siberian Federal University and the University of Göttingen Konstantin Krutovsky believes that there is a sense in Alexander Panchin's reasoning, however, the authors still did not specifically select the distribution of these restriction sites - they are indeed often used by genetic engineers to cut and stitch DNA fragments using special enzymes - restrictase.
“The fact that these sites are found in natural viruses is an insufficient argument – we need to compare not just the occurrence, but the probability of a random coincidence of the distributions of these sites in the compared genomes,” says Krutovsky. “The sites in question in this preprint are indeed suspiciously evenly distributed, and their locations in the genome correspond to fragment sizes that are often used by genetic engineers, as shown in publications on synthetic viruses.”
In addition, according to Krutovsky, it would be interesting how Alexander Panchin and other well-known bioinformaticians would explain the abnormally high frequency of synonymous (single-valued) nucleotide positions noted by the authors of the preprint, and what is the probability that this is an accident. “That is, it looks as if those who designed this virus deliberately tried not to disrupt the amino acid sequence at these restriction sites in the genes encoding proteins,” the expert says.
Professor Krutovsky believes that "this work (preprint) did not put an end to the search for the source of the current COVID-19 pandemic and did not answer categorically and unambiguously the question of the artificiality of the coronavirus, but it still raises additional doubts about its natural origin."
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