Meet ACE2, the Enzyme at the Center of the Covid-19 Mystery

During the first chaotic months of the Covid-19 pandemic, it was already clear that the novel coronavirus spreading around the world didn’t affect everyone equally. The earliest clinical data out of China showed that some people consistently fared worse than others, notably men, the elderly, and smokers. It made some scientists wonder: What if the elevated risk of severe infection and death shared by these different people all boils down to differences in a single protein?

Jason Sheltzer, a molecular biologist at Cold Spring Harbor Laboratory, started talking about this possibility with his partner, Joan Smith, a software engineer at Google, during the early days of their New York lockdown. “We thought maybe the simplest explanation could be if all these factors affected the expression of ACE2,” says Sheltzer.

ACE2, which stands for angiotensin-converting enzyme 2, is a protein that sits on the surface of many types of cells in the human body, including in the heart, gut, lungs, and inside the nose. It’s a key cog in a biochemical pathway that regulates blood pressure, wound healing, and inflammation. ACE2’s amino acids form a grooved pocket, allowing it to snag and chop up a destructive protein called angiotensin II, which drives up blood pressure and damages tissues. But angiotensin II isn’t the only thing that fits in ACE2’s pocket. So does the tip of the mace-like spike proteins that project from SARS-CoV-2, the coronavirus that causes Covid-19. Like a key turning in a latch, the virus gains entry to the cell through ACE2, then hijacks the cell’s protein-making machinery to make copies of itself. An infection begins.