Covid-19: analysis of the genome would reveal a double origin of the virus

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The SARS-CoV-2 virus responsible for the Covid-19 pandemic is the subject of numerous genetic analyzes worldwide to understand its origin and evolution. Although the number of scientific articles on this virus continues to increase, there are still many gray areas regarding the origin of this virus.

In December 2019, 27 of the first 41 people hospitalized (66%) went through a market located in the heart of Wuhan City, in Hubei Province. But the origin of the epidemic is probably not related to contact with live or dead animals present in this market, because it seems, according to a Chinese study conducted at the Wuhan hospital, that the first identified human case did not visit this market.

According to this hypothesis, the molecular dates estimated from the SARS-CoV-2 genomic sequences indicate an origin in November. Therefore, we have the right to ask ourselves about the link between this Covid-19 epidemic and wildlife.

What we know thanks to the genomic data of the Betacoronavirus

The SARS-CoV-2 genome was quickly sequenced by Chinese researchers. It is an approximately 30,000 base RNA molecule that contains 15 genes, including the S gene that encodes a protein located on the surface of the viral envelope (by comparison, our genome is in the form of a DNA double helix about the size of 3 billion bases and contains almost 30,000 genes).

Comparative genomic analyzes have shown that SARS-CoV-2 belongs to the Betacoronavirus group and that it is very close to SARS-CoV, responsible for an acute pneumonia epidemic that appeared in November 2002 in the Chinese province of Guangdong, which later it spread to 29 countries, especially France in 2003.

A total of 8098 cases were recorded, including 774 deaths. Bats of the genus Rhinolophus (potentially several cave species) are known to have been the reservoir for this virus and that a small carnivore, the palm civet (Paguma larvata), may have served as an intermediate host between bats and early cases. humans.

Since then, many Betacoronaviruses have been discovered, mainly in bats, but also in humans. Therefore, the RaTG13 virus, isolated from a bat of the species Rhinolophus affinis collected in the Chinese province of Yunan, has recently been described as very close to SARS-CoV-2, the sequences of its genome are 96% identical. These results indicate that bats, and particularly the species of the genus Rhinolophus, constitute the reservoir of the SARS-CoV and SARS-CoV-2 viruses.

But how is a tank defined? It is one or more animal species with little or no virus sensitivity, which will naturally harbor one or more viruses. The absence of symptoms of the disease is explained by the efficiency of their immune system that allows them to fight against excess viral proliferation.

Recombination mechanism

On February 7, 2020, we learned that a virus even closer to SARS-CoV-2 had been discovered in the pangolin. With 99% identity announced, this made it a more likely reservoir than bats. However, a more recent study, currently under investigation, suggests a much more complex situation. Finally, the genome of the Malaysian pangolin coronavirus (Manis javanica) is generally not that close to SARS-Cov-2, with only 90% identity. Therefore, it is not responsible for the current epidemic.

That said, the virus isolated from pangolin has a 99% identity with SARS-Cov-2 if we compare the 74 amino acids of a particular region of protein S, the ACE2 receptor binding domain (angiotensin-converting enzyme 2) that allows for the virus to enter human cells to infect them. In the same region, the RaTG13 virus isolated from the R. affinis bat is highly divergent (77%).

For simplicity, this means that the coronavirus isolated from the pangolin can enter human cells, while the one isolated from the bat R. affinis cannot. Furthermore, this suggests that the SARS-Cov-2 virus is the result of a recombination between two different viruses, one close to RaTG13 and the other closer to the pangolin virus. In other words, it is a chimera between two pre-existing viruses.

This recombination mechanism has already been described in coronaviruses, in particular to explain the origin of SARS-Cov. It is important to know that recombination results in a new virus potentially capable of infecting a new host species. For recombination to occur, the two diverging viruses must have infected the same organism concomitantly.

Two unanswered questions remain: in which organism did this recombination take place? (A bat, a pangolin, or another species?) And, above all, under what conditions did this recombination take place on?

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