A new coronavirus discovered in a Brazilian bat provides more support for the theory that the Sars-CoV-2 coronavirus, which caused the Covid-19 pandemic, evolved naturally in bats, as opposed to the controversial claim that it was engineered in a Chinese lab.
One of the key characteristics of Sars-CoV-2 that meant that it was so infectious was that it possesses a furin cleavage site (FCS) on its surface spike proteins. This means the spikes can bind to the enzyme furin protease, which is present throughout the body, and this helps split the spike proteins more easily – a process that enables the virus to fuse with and infect cells.
While the FCS was known to exist in other coronaviruses, some researchers thought its presence in Sars-CoV-2 was unusual. The prevailing view was that Sars-CoV-2 jumped from bats to humans, possibly in the Wuhan meat markets, however the FCS had not been seen in other bat-derived Sars-related coronaviruses before. In early 2021, this helped to fuel an alternative “lab leak” hypothesis suggesting the pathogen might have originated in a Chinese lab.
‘It is understandable why suspicion exists,’ says Markus Hoffmann who co-discovered the key role of the furin cleavage site for Sars-CoV-2 infection at the German Primate Center, Germany. ‘The outbreak started in a city, Wuhan, with a virology lab specialised in bat coronaviruses. Further, past research proposals discussed adding multibasic [composed of multiple amino acid residues] cleavage sites to bat viruses. Yet these factors may be circumstantial rather than evidence of engineering.’
Now, an international team of researchers has discovered a previously unknown coronavirus in a Parnell’s moustached bat (Pteronotus parnellii) native to the Americas. After sequencing its genome, they found it is a betacoronavirus, one of the main groups of coronavirus, which includes Sars-CoV-2 and Mers-CoV, that infect humans.
However, while the Brazilian coronavirus species is phylogenetically distinct from known betacoronaviruses, belonging to its own subgenera and only distantly related to Sars-CoV-2, the team discovered it too has an FCS. Intriguingly, the four amino acid sequence of its FCS differs from that found in Sars-CoV-2 by only one amino acid.
‘Our study tells us is that there are still many diverse coronaviruses in nature that we know very little about,’ says Kosuke Takada at the University of Osaka, Japan. ‘Our finding simply shows that a functional furin cleavage site can be present in a bat betacoronavirus found in nature that is phylogenetically distant from Sars-CoV-2.’ However, the researchers stress that firm conclusions cannot be made from their study with regard to the origins Sars-CoV-2.
‘While the current study does not provide direct proof or disproof of a natural origin of Sars-CoV-2 with respect to the multibasic cleavage site in the spike protein, it highlights that multibasic cleavage sites in spike proteins can be naturally found in diverse coronaviruses from multiple phylogenetic groups,’ says Hoffman, who was not involved in the work. ‘Based on what we know about Sars-CoV-2 and other coronaviruses, a natural origin appears to me as a plausible scenario. For me, there is currently no compelling evidence that Sars-CoV-2 was engineered in a lab.’
Meanwhile, it remains unknown if the latest coronavirus poses any risk to humans. Although it possesses an FCS, this feature alone does not mean it can infect humans and spread, explains Takada. Other coronaviruses have FCSs and cannot infect humans.
Experimental work is needed to address the zoonotic potential for the newly discovered Brazilian coronavirus to spread from bats to humans, says Hoffman. ‘This includes experiments that determine the ability of the spike protein to bind to receptor molecules on human cells,’ he explains. ‘While a multitude of coronaviruses has been identified in bats over the past 25 years, only a minor fraction of them has a spike protein capable of binding to receptor molecules on human cells.’
