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Covid-19 lineage circulating in bats for up to 70 years

The coronavirus causing the current pandemic which has killed more than 650,000 people around the world may have first evolved in bats in 1948, a study claims. 

Academics made the discovery as part of a research project investigating the ancestral origins of the SARS-CoV-2 virus, which causes Covid-19. 

Scientists led by the Pennsylvania State University compared the Covid-causing pathogen to its closest relatives found in bats. 

Previous research has identified horseshoe bats as a reservoir of coronaviruses and the likely original source of SARS-CoV-2. 

  

Tracking the evolution of the virus through time is difficult, as coronaviruses often share genetic information and mutate in a process called recombination.

However, researchers found three sections of the virus’s genetic information, which appear to have been left untouched by recombination. 

Analysis of these sections reveals SARS-CoV-2 and its closest relative in bats, called RaTG13, share a common ancestor.   

The question remains as to when the deadly SARS-CoV-2 split from all the other coronaviruses, which live in ‘endemic equilibrium with their natural host species, horseshoe bats’.  

Because the scientists studied three sections of DNA, they got three different dates for when the virus diverged from its ancestral lineage of sarbecoviruses, the subgroup of coronavirus to which SARS-CoV-2 belongs.

These dates were 1948, 1969 and 1982, ‘indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades’, the researchers write in their study, published in Nature Microbiology.  

It also found that SARS-CoV-2 is 96 per cent similar to RaTG13 which was found in a bat in 2013 and diverged from this sister strand in 1969. 

The researchers warn that the virus has existed for between 40 and 70 years and therefore bats may well contain other coronaviruses which can infect humans. 

As well as looking at how long the virus dates back in bats, the researchers tried to clear up the murky picture as to how it entered humans. 

It is known from previous studies that the virus enters humans thanks to a specific site on the virus’s surface spike, known as a receptor-binding domain (RBD).

This allows the spike of the virus to latch on to the ACE2 receptor on human cells and unlocks the body’s defences, allowing the virus to wreak havoc. 

However, of the dozens of coronaviruses previously identified in bats, not a single other sarbecovirus has been found with the unique RBD, not even RaTG13.

The nearest thing to the RBD of SARS-CoV-2 on other viruses is seen in pangolins. 

Previously, this fact had been used to incriminate pangolins as the intermediary host which acted as a stepping stone in allowing the virus to hop from bats to humans.  

But according to the latest research, that is unlikely.

Instead, pangolins are in the same boat as humans and RaTG13 did have the ability to infect humans when the two viruses diverged. 

However, after the two viruses split, RaTG13 then likely mutated and nullified its ability to infect human cells. 

David L Robertson, professor of computational virology at the MRC-University of Glasgow Centre for Virus Research, said: ‘SARS-CoV-2’s receptor-binding domain sequence has so far only been found in a few pangolin viruses.

‘While it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans. 

‘Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins.’

Professor Mark Pagel from the University of Reading, who was not involved in the study, says pangolins were suspected due to their popularity in wet markets as sources of materials for traditional medicine.    

‘The variable loop region of the important spike protein [in pangolins] is more closely related to SARS-CoV-2 than is the variable loop region of  RaTG13,’ he says.

‘The authors’ analysis shows that the difference between RaTG13 and SARS-CoV-2 in the critical variable loop region probably arose in RaTG13 after it separated from the common ancestor.

‘This then points to the conclusion that there are as yet undetected horseshoe bat viruses that are the likely source of Covid-19 — ones that have not been altered like RaTG13 has.’

The academics say that this study again highlights the dangers posed by zoonotic diseases, where a pathogen jumps from one species to another. 

Bats have evolved over centuries to live unaffected by dozens of coronaviruses, but any number of them could be fatal and highly infectious to humans.  

Maciej Boni, associate professor of biology at Penn State, warns the Covid-19 pandemic ‘will not be our last’.

He said: ‘Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus’s genome can be derived from multiple sources.

‘This has made it difficult to reconstruct SARS-CoV-2’s origins – you have to identify all the regions that have been recombining and trace their histories.

‘We put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution.’

He added: ‘We were too late in responding to the initial SARS-CoV-2 outbreak but this will not be our last coronavirus pandemic.

‘A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits.’

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