The most intensely scrutinized genetic feature is something called a furin cleavage site, a small insertion in the spike protein that helps the virus enter human cells efficiently. SARS-CoV-2 has a unique four-unit insertion at a critical junction in its spike protein that no other known virus in its family (sarbecoviruses) possesses. Similar features exist in other, more distantly related coronaviruses like MERS, so the structure itself isn’t biologically impossible through natural evolution. But its appearance in SARS-CoV-2 is unusual enough to draw attention from both camps.

Some scientists note that this insertion uses a specific genetic spelling (a CGG-CGG codon pair) that appears with only about 5% frequency in similar viruses, making some researchers argue it looks engineered. Others counter that rare codons do occur naturally and that evolution produces unexpected outcomes all the time. Critically, researchers have pointed out that the techniques used in coronavirus research could produce modifications “practically indistinguishable from a rare coronavirus with a naturally emerging” cleavage site. In other words, if someone did insert it in a lab, there might be no way to tell from the genome alone.

Why a Lab Leak Remains Plausible
The Wuhan Institute of Virology, located roughly 10 miles from the Huanan market, housed one of the world’s largest collections of bat coronaviruses and was actively studying them. Researchers there had collected samples from bat caves across southern China, including the cave where RaTG13 was found, and had published research on engineering chimeric coronaviruses to study their potential to infect human cells. A 2018 grant proposal from the institute’s U.S. collaborators described plans to insert furin cleavage sites into SARS-related coronaviruses, though there is no public evidence that this specific work was carried out.