The deadly SARS-CoV-2 virus has possibly emerged from shuffling and selection of viral genes across different species like bats and pangolins before it reaches humans, new research has claimed.
A combination of genetic shuffling and evolutionary selection of near-identical genetic sequences among specific bat and pangolin coronaviruses may have led to the evolution of SARS-CoV-2 and its introduction into humans, said the team led by Duke University in North Carolina.
Published in the peer-reviewed journal Science Advances, the study showed that the virus’ entire receptor binding motif (RBM), a component that plays a key role in viral entry into host cells, was introduced through recombination with pangolin coronaviruses.
Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine.
“We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin, and human coronaviruses, suggesting similar evolutionary constraints in different host species,” explained Xiaojun Li, the lead researcher from Duke University.
“We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans,” he added.
The study joins ongoing efforts to identify the source of the virus that causes COVID-19.
“Proximity of different species in a wet market setting, for example, may increase the potential for cross-species spillover infections, by enabling recombination between more distant coronaviruses and the emergence of mutations,” the authors wrote.
By analyzing 43 complete genome sequences from three strains of SARS-CoV-2-like coronaviruses from bats and pangolins, Li and colleagues delineated which strains were most and least similar to the novel coronavirus, with a special focus on genes related to the virus’ spike protein complex, – a critical component that facilitates viral entry into host cells.
They found evidence of strong evolutionary selection around the RBM among the bat, pangolin, and human coronaviruses they studied.
Amino acid sequences from these viruses and SARS-CoV-2 were identical or nearly identical in the regions adjacent to the RBM, suggesting that common evolutionary mechanisms shaped these distinct viral strains.
Together, evolutionary selection and frequent recombination among coronaviruses from bats, pangolins, and humans may have allowed the closely related viruses to readily jump between species, leading to the introduction of SARS-CoV-2 in humans.
While the precise origin of SARS-CoV-2 remains a mystery, this study makes clear “that reducing or eliminating direct human contact with wild animals is critical to preventing new coronavirus zoonoses in the future”.