Over the course of several weeks, we all learned a lot about COVID-19 and the coronavirus that causes it: SARS-CoV-2. While the number of scientific articles on this virus is increasing, there are still many gray areas regarding its origin.
In what animal species did it arise? A bat, pangolin, or other wild species? Where did he come from? From a cave or forest in the Chinese province of Hubei or from somewhere else?
In December 2019, 27 of the first 41 hospitalized (66 percent) attended a market located in downtown Wuhan in Hubei province. But, according to a study from Wuhan Hospital, the very first patient identified did not visit this market.
Instead, a molecular dating estimate based on the genomic sequences of SARS-CoV-2 points to the emergence of the virus in November. This raises questions about the link between this COVID-19 epidemic and wildlife.
Genome data.
The SARS-CoV-2 genome was quickly sequenced by Chinese researchers. It is an RNA molecule of about 30,000 bases, containing 15 genes, including the S gene, which encodes a protein located on the surface of the viral envelope (by comparison, our genome is in the form of a DNA double helix with about 3 billion bases in size and contains about 30,000 genes).
Comparative genomic analysis showed that SARS-CoV-2 belongs to the group of beta-coronaviruses and that it is very close to SARS-CoV, which is responsible for the epidemic of acute pneumonia, which appeared in November 2002 in the Chinese province of Guangdong and then spread to 29 countries in 2003 year.
A total of 8098 cases were registered, including 774 deaths. It is known that it was carried by bats of the genus Rhinolophus, and that a small predator, the palm civet (Paguma larvata), may have served as an intermediate host between bats and early human cases.
Since then, many beta coronaviruses have been found mainly in bats, but also in humans. For example, RaTG13, isolated from a bat of the species Rhinolophus affinis, in the Chinese province of Yunan, has recently been described as very similar to SARS-CoV-2, with genome sequences identical to 96 percent.
These results indicate that bats, and in particular species of the genus Rhinolophus, are a reservoir of SARS-CoV and SARS-CoV-2 viruses.
A reservoir is one or more animal species that are not very susceptible to the virus, which will naturally harbor one or more viruses.
The lack of symptoms of the disease is due to the effectiveness of their immune systems, which allows them to fight the over-spread of the virus.
Recombination mechanism.
On February 7, 2020, we learned that pangolin was found to have a virus even closer to SARS-CoV-2. With 99 percent genome matching, it suggested a more likely vector than bats.
A recent study shows that the genome of the coronavirus isolated from the Malaysian pangolin (Manis javanica) is less similar to SARS-Cov-2, with only 90 percent genome consistency. This indicates that the virus isolated from the pangolin is not responsible for the COVID-19 epidemic that is currently raging.
However, the coronavirus isolated from pangolin is 99 percent similar in a specific region of the S protein, which corresponds to the 74 amino acids involved in the ACE (angiotensin converting enzyme 2) receptor binding domain, which allows the virus to invade human cells to infect them.
In contrast, the RaTG13 virus isolated from R. affinis bats is very different in this particular region (only 77 percent similarity). This means that the coronavirus isolated from pangolin is able to enter human cells, while the coronavirus isolated from the R. affinis bat is not.
In addition, these genomic comparisons indicate 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 pangolin virus. In other words, it is a 'chimera' between two pre-existing viruses.
This recombination mechanism has already been studied, in part 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 take place, two different viruses had to infect the same organism at the same time.
Two questions remain unanswered: in which organism did this recombination take place? (bat, lizard or other species?) And, first of all, under what conditions did this recombination take place?
Alexander Khasanin, Systems Institute, Evolution, Biodiversity (CNRS, MNHN, SU, EPHE, UA), National Museum of Natural History (MNHN).
Article published by The Conversation.
Sources: Photo: (xia yuan / Getty Images)
