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In a finding that may put to rest all conspiracy theories around the origin of the current Covid-19 pandemic, which so far claimed more than 6.58 lakh lives globally, an international team of scientists has found that the virus SARS-CoV-2 in all likelihood would have diverged from the most closely related bat viruses approximately 40–70 years ago.
In a paper published in the journal Nature Microbiology on Tuesday, the scientists led by Maciej Boni at Pensylvania State University in the US and Philippe Lemey at KU Leuven in Belgium suggested the lineage that gave rise to SARS-CoV-2 may have been circulating in bats for decades. Apart from them, scientists from other institutions in China, the UK and the US participated in the study.
The findings from the study may discredit the contention that the virus was genetically manipulated one which escaped from a viral research lab accidentally.
Understanding the evolutionary history of SARS-CoV-2 has been difficult because coronaviruses are known to recombine (exchange genetic material between different viruses) and small genomic subregions of the virus may have different ancestries.
However, studies in the past have identified a bat virus named RaTG13 as the most closely related virus to SARS-CoV-2, suggesting that a bat origin for the Covid-19 outbreak is likely. However, research has also identified similar coronaviruses in pangolins (particularly, a pangolin virus isolated in Guangdong in 2019 and named Pangolin-2019) and it has been proposed that they may have been an intermediary host. However, the current study raised doubts about such a possibility.
Three approaches
Boni and colleagues analysed the evolutionary history of SARS-CoV-2 using genomic data on sarbecoviruses (the subgenus to which SARS-CoV-2 belongs) employing three distinct approaches to identify regions in the virus that had not undergone recombination and thus could be used to reconstruct its evolution.
All three approaches suggested that RaTG13 and SARS-CoV-2 share a single ancestral lineage. Moreover, they estimated that SARS-CoV-2 genetically diverged from related bat sarbecoviruses in 1948, 1969 and 1982, respectively.
The authors also examined the receptor-binding domain (RBD) of the virus spike protein, which enables the virus to use the human ACE2 receptor – a protein on the surface of the lung cells -- to enter cells. Although this has been shown to be genetically more similar to pangolin viruses than RaTG13, the authors found that the spike protein did not show evidence of rearrangement of genetic material taking place between the lineage leading to SARS-CoV-2 and other known sarbecoviruses.
Long divergence
The authors argued that the long divergence period of SARS-CoV-2 indicates there may have been unsampled virus lineages in bats that had potential to jump to humans due to the ancestral position of human-adapted contact residues on the SARS-CoV-2 RBD, but said better sampling was needed to assess this.
They argued that existing diversity and the dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with the potential to cause significant human outbreaks before they emerge, underscoring the need for real-time human disease surveillance systems that can rapidly identify and classify pathogens.