More furin cuts mean more spike proteins primed to enter human cells. In SARS-CoV, less than 10% of spike proteins are primed, says Menachery, whose lab group has been quantifying the primed spike proteins but is yet to publish this work. In SARS-CoV-2, that percentage rises to 50%. In the Alpha variant, it’s more than 50%. In the highly transmissible Delta variant, the group has found, greater than 75% of spikes are primed to infect a human cell.
Known unknowns
The scientific community is still scratching the surface of its understanding of SARS-CoV-2. Key unknowns include the number of ACE2 receptors needed to bind to each spike protein; when exactly the S2 site is cleaved by TMPRSS2; and the number of spikes needed for virus–cell membrane fusion, says McLellan — and that’s just for entry. In April 2020, a team at the University of California, San Francisco, identified at least 332 interactions between SARS-CoV-2 and human proteins25.
It is not easy to keep pace with the quickly mutating virus. Most mutations so far are associated with how effectively the virus spreads, not with how much the virus damages the host, experts agree. This month, a study reported that the Delta variant grew more rapidly and at higher levels inside people’s lungs and throats than did earlier versions of the virus26.
But it is not yet certain how Delta’s mutations have supercharged the variant in this way, says Stern-Ginossar. “This is something many labs are trying to figure out.”
