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In a study published in Nature on Wednesday, researchers from the UK and Kenya analysed the spike proteins of coronaviruses carried by bats in Kenya. It is these “receptor binding” areas which coronaviruses use to enter and infect human cells.
They found that a coronavirus, dubbed CcCoV-KY43, which was found in heart-nosed bats in southeastern Kenya, has evolved a new way of binding to human cells; one that is distinct from the mechanism used by SARS-COV-2, the coronavirus responsible for the Covid-19 pandemic.
While there is no evidence the virus has jumped to people yet, the findings have implications for pandemic preparedness in Kenya and around the world.
It suggests that the Kenyan virus itself could pose a threat and that coronaviruses generally could evolve multiple different ways of attacking animal cells.
“Now that we’re aware that there is a potential risk here, a risk that has always existed … we can start to prepare for it,” said Prof Stephen Graham, professor of virus-host interactions at the University of Cambridge and co-author of the report.
“The risk is there. It’s like crossing the road – I’d rather do it with my eyes open,” he said.
The discovery came after scientists set out to better understand and characterise the spike proteins in alphacoronavirus. Unlike betacoronaviruses – which include Sars-Cov-2 – there has been little research into alphacoronaviruses.
The scientists began by identifying some 2,000 coronavirus virus sequences that had already been published in a public database called Genbank. Next, they used a computational approach to narrow this down to 40 spike proteins that reflect alphacoronaviruses’ genetic diversity.
The spikes were incorporated into lab-safe pseudoviruses, then tested against libraries of known coronavirus receptors from different species. The vast majority did not have receptor binding domains that could infect people – CcCoV-KY43 was the one exception.
“What is very nice about this elegant work is that all the discoveries were made without the need to work with any dangerous viruses,” said Prof Wendy Barclay, a professor of infectious disease at Imperial College London, who was not involved in the study.
“The scientists used a state of the art approach taking sequences derived from the original bat samples in Kenya to recreate surrogates that mimic the virus but are not infectious to humans. The use of a platform to scan a huge range of potential human receptors is also a big advance here.”
The researchers said the work also provides a blueprint for identifying and preparing for a potential spillover event before it emerges – blood samples taken in southeastern Kenya suggest people have not been exposed to the virus. In the past, receptor binding domains have been studied only after a virus has jumped into people.
“This is not a new Covid-19, there are many steps after entry that are needed for a virus to be able to replicate in the human cell, and then release [and spread],” Dr Dalan Bailey, a specialist in the molecular biology of RNA viruses at The Pirbright Institute, told a briefing.
“We don’t have evidence that this virus has spilled into human populations in Kenya, but we’re now in a much better position to start preparing for that potential risk,” he added. “Outbreak prevention starts with understanding risk.”
Prof Stuart Neil, head of the Department of Infectious Diseases at King’s College London and not involved in the research, said it was an interesting study that highlights “the incredible plasticity in these viruses and why we need to keep an eye on them”.
But he added that there are still more questions to answer to fully understand the risk – including whether CcCoV-KY43 can actually replicate and grow inside humans, and whether it has jumped from bats to other local mammals in Kenya.
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