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

In the space of a few weeks, we have all learned a lot, but also heard quite a few rumors about the Covid-19 disease and the virus responsible: SARS-CoV-2. While the number of scientific articles on this virus continues to increase, there are still many gray areas as to the origin of this virus.

Dn what animal species did it appear? A bat, a pangolin, or some other wildlife? Where is he from ? From a cave or a forest in the Chinese province of Hubei or elsewhere? In December 2019, 27 of the first 41 people hospitalized (66%) passed through a market located in the heart of the city of Wuhan, in Hubei province. But the origin of the epidemic is probably not linked to contacts with living or dead animals present in this market, as it appears, according to a Chinese study conducted at the Wuhan hospital, that the very first human case identified did not visit this market.

In accordance with this hypothesis, the molecular dating estimated from the genomic sequences of SARS-CoV-2 rather indicate an origin in November. We are therefore entitled to wonder about the link between this Covid-19 epidemic and wildlife.

What we know from genomic data on betacoronavirus

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

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

A total of 8098 cases were recorded, including 774 deaths. We know that bats of the genus rhinolophus (potentially several cave species) were the reservoir of this virus and that a small carnivore, the palm civet (Paguma larvata), could have served asintermediate host between bats and early human cases.

Since then, many betacoronavirus have been discovered, mainly in bats, but also in humans. This is how the RaTG13 virus, isolated from a bat of the species Rhinolophus affinis collected in the Chinese province of Yunan, was recently described as very close to SARS-CoV-2, the sequences of their genome being 96% identical. These results indicate that bats, and in particular species of the genus rhinolophus, constitute the reservoir of the SARS-CoV and SARS-CoV-2 viruses.

Bat, Rhinolophus affinis.
Alexandre Hassanin, Author provided

But how do you define a reservoir? This is one or more animal species with little or no sensitivity to the virus, which will naturally harbor one or more viruses. The absence of symptoms of the disease is explained by the efficiency of their immune system which allows them to fight against too much 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 advertised, this made it a more likely reservoir than bats. A more recent study, currently under appraisal, nevertheless suggests a much more complex situation. Finally, the genome of the coronavirus isolated from the Malay pangolin (Manis javanica) is not overall that close to SARS-Cov-2, with only 90% identity. He is therefore not responsible for the current epidemic.

That said, the virus isolated from pangolin does exhibit 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 the virus to enter human cells to infect them. In the same region, the RaTG13 virus isolated from bats R. affinis is very divergent (77%).

To put it simply, this means that the coronavirus isolated from pangolin is able to enter human cells while that isolated from bats R. affinis is not. Moreover, 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 that of pangolin. In other words, it is a chimera between two pre-existing viruses.

This recombination mechanism had 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 divergent viruses must have infected the same organism concomitantly.

Two questions remain unanswered: 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?The Conversation

Alexandre Hassanin, Associate Professor (HDR) in evolutionary biology at Sorbonne University, National Museum of Natural History (MNHN)

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.

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