Where does SARS-CoV-2 come from? It is a question that has preoccupied researchers since the end of last year. It soon became clear that the virus originated in bats. The virus is believed to have passed from bats to humans, perhaps through an intermediate host, such as the pangolin. And then because it was able to jump from person to person, having conquered the world.
No intermediate host
A new study now partially endorses this hypothesis (see box). Yes, the virus comes from bats. But no, the virus did not need an intermediate host to develop into the virus that terrifies people today.
Instead, family members of SARS-CoV-2 – who are also capable of infecting humans – have been circulating among bats for decades. That can be read in the magazine Nature Microbiology.
Earlier research has shown that the virus RaTG13 – which occurs among horseshoe noses – was closely related to SARS-CoV-2. Both viruses are 96% the same genetically. It seems to indicate that SARS-CoV-2 has jumped from bats to humans. But some researchers believe that the pangolin also played a role. Not only because these animals are widely found in Chinese markets, but also because the spike protein of coronaviruses circulating among pangolins has more similarities to that of SARS-CoV-2 than RaTG13. It led to the hypothesis that although SARS-CoV-2 comes from bats, it evolved in pangolins to a virus that is highly capable of penetrating human cells.
Thus, the new research reveals that pangolins have played no significant role in the evolutionary history of SARS-CoV-2. The researchers draw that conclusion after studying the genome of SARS-CoV-2 and compared it to that of closely related SARS-CoV-2 coronaviruses found in bats and pangolins. In order to get a good picture of the evolutionary history of SARS-CoV-2, they excluded so-called recombinant regions. These are regions in the sequence of the coronaviruses that are believed to exchange information when the viruses are in the same host. “Coronaviruses have highly recombinant genetic material, meaning that different parts of the virus’s genome may come from multiple sources,” explains researcher Maciej Boni. “That makes it difficult to reconstruct the origin of SARS-CoV-2. After all, you have to identify all regions that have been recombined and find out their history. ” By focusing on non-recombinant regions, the researchers have therefore been able to gain a clearer picture of the evolutionary history of SARS-CoV-2.
The research shows that the lineage, which also includes SARS-CoV-2, separated from the lineage of other bat viruses between 40 and 70 years ago. It means that family members of SARS-CoV-2 have been circulating under bats for decades. More importantly, the researchers show that one of the older properties that SARS-CoV-2 has in common with these family members is the so-called Receptor-Binding Domain (RBD) on the spike protein. It is this part of the spike protein characteristic of coronaviruses that enables SARS-CoV-2 to infect human cells. It reveals that coronaviruses in bats have evolved into viruses that can infect humans. Therefore, no pangolins have been involved. “While it is possible that pangolins have been an intermediate host and have transferred SARS-CoV-2 via pangolins to humans, there is no evidence that pangolins need to be infected to allow the passage of bat viruses to humans,” explains researcher David Robertson.
But what about RaTG13? The coronavirus so closely related to SARS-CoV-2 whose spike proteins on a crucial part of it are less similar to those of SARS-CoV-2 than those of pangolins? The researchers think they can explain that. They argue that RaTG13 has changed after breaking away from the ancestor sharing the virus with SARS-CoV-2. “This leads to the conclusion that there are still undiscovered bat viruses from which SARS-CoV-2 descended and that have not changed – like RaTG13 -” says Professor Mark Pagel, an evolutionary biologist at Reading University who is not involved in this research. Detecting those viruses, which are even more closely related to SARS-CoV-2 than RaTG13, is necessary to get an even more complete picture of the evolution of the virus. But it will not be easy. “During a previous epidemic – the SARS outbreak – researchers have searched for more than 14 years before finding its suspected origin, also in horseshoe noses.”
The study not only provides more insight into the evolutionary history of SARS-CoV-2, but also reveals the importance of closely monitoring bats and the viruses they harbor. Because SARS-CoV-2 has relatives based on this study, who are also able to infect people. And those viruses are still circulating undetected under bats. Pagel: “The researchers’ analysis suggests that coronaviruses capable of infecting humans have been present in bats for 40 to 70 years, but have remained undetected. That just goes to show the scale and nature of the problem that zoonotic transmission poses to humans: innumerable undetected viruses capable of infecting humans can live in animals. ” It requires vigilance. “What is important for successful surveillance is knowing what viruses to look out for and focusing on viruses that can already infect people,” said Robertson. “We should have been better prepared for a second SARS virus.” Boni endorses that. “We responded too late to this SARS-CoV-2 outbreak, but this is not our latest coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be in place to get a handle on viruses like SARS-CoV-2 when the number of contamination cases is still limited. ”
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