18 Jan 2021
Researchers at The Pirbright Insititute identify key differences in SARS-CoV-2 that may be responsible for the jump from bats to humans.
James Westgate
Job Title
Veterinary scientists have moved a step closer to finding the mechanism that allowed SARS-CoV-2 to jump to humans.
The virus that causes COVID-19 is thought to have originated in bats and the closest known relative is a bat coronavirus – RaTG13. But how it jumped hosts to infect humans is unclear, as is the potential for the virus to infect other animal species.
Knowing exactly how such viruses become zoonotic could be the key to preventing future pandemics.
Now researchers from The Pirbright Institute have moved a step closer to the answer by identifying key differences in SARS-CoV-2 that may be responsible for the jump from bats to humans, as well as establishing which animals have cellular receptors that allow the virus to enter most effectively.
The team compared the genomes of both viruses and identified several important regions that differed between their spike proteins, which the virus uses to bind to the angiotensin-converting enzyme 2 (ACE2) surface receptors of cells to gain entry to a host.
They then examined whether these differences were involved in the adaptation of SARS-CoV-2 to humans and found these genetic adaptations were similar to those made by SARS-CoV when it adapted from bats to infect humans.
This suggests a common mechanism may exist by which this family of viruses mutates to jump from animals to humans and identifying it could help ward off another pandemic.
Dalan Bailey, head of the viral glycoproteins group at Pirbright, said: “Using molecular techniques to study coronavirus spike proteins in isolation, without ever needing to work with the SARS-CoV-2 virus, has enabled us to take an in-depth look at how genetic differences in coronavirus spike proteins and animal ACE receptors influence which animals the virus may be able to infect.
“Uncovering the common traits that allow viruses to jump between animals and humans helps us to identify potential reservoirs of disease and forewarn us of future threats.”
Knowing more about the mechanism that enables certain viruses to become zoonotic is crucial when it comes to the coronavirus family, according to Dr Bailey.
He added: “MERS-CoV has already made the same switch with camels acting as an intermediate host and there are likely to be other coronaviruses with a similar propensity to switch hosts that are already circulating in the wild – for example, in bats.
“We know that bats have lots of coronaviruses (from sampling studies) and we know that bats represent around 20 per cent of mammal species, so in some ways it’s a numbers problem. There are just lots of bats and therefore lots of bat coronaviruses.”
Researchers also investigated whether the SARS-CoV-2 spike protein could bind to the ACE receptors from different animals to ascertain which may be susceptible to infection.
Dog, cat and cattle ACE receptors were identified as the strongest interactors with the SARS-CoV-2 spike protein.
Commenting on the implications of the findings, Dr Bailey made it clear that entry into a host is only one step in the viral replication cycle and other factors play an important role in determining whether one animal or another gets disease or transmits the virus.
He added: “Interestingly, while dog ACE was shown to be highly permissive for SARS-CoV-2 spike binding in our studies, these animals are either mildly or subclinically infected when challenged or naturally infected with the virus.
“An animal’s susceptibility to infection and its subsequent ability to infect others is reliant on a range of factors, including whether SARS-CoV-2 is able to replicate once inside cells and the animal’s ability to fight off the virus.
“Further studies are needed to understand whether livestock and companion animals could be receptive to COVID-19 infection from humans and act as reservoirs for this disease.”
