What is a furin cleavage site, why is it important, and how might this have arisen in SARS-CoV-2?

There is no consensus among scientists on the origin of SARS-CoV-2. One aspect of the virus that has been much discussed is the so-called “furin cleavage site” (FCS). Here we explain the structure and function of the FCS and its significance in SARS-CoV-2. The existing data suggest that the FCS of SARS-CoV-2, which remains unique among the hundreds of sarbecoviruses sampled around the world, is fully functional and is consistent with the properties of FCS in many other substrates of this protease. Three possible routes have been proposed for how the FCS appeared in SARS-CoV-2: natural recombination, serial passage in cell culture or in an animal host and laboratory insertion via gene engineering. Here we review the merits and limitations of each proposal. All three proposals are limited by the absence to date of an immediate precursor virus. We renew our call that virus databases, lab notebooks and electronic communications be made available for independent scrutiny as part of a bipartisan investigation into the origins of COVID-19.