COVID-19: Separating Fact from Fiction

by Anirban Mahapatra

Instead of trying to block the spike from binding to the ACE2 receptor, some researchers have taken a different tact altogether. They are experimenting with creating decoy ACE2 that the virus sticks to instead of actual cellular ACE2 receptors that let it inside cells.25 A drug company is using this strategy in the hope that flooding the body with soluble ACE2 receptors will fool the virus into attaching to it, instead of to the ones on actual cells. The goal here is to saturate virus particles with something that renders them ineffective in infecting cells.26 A similar strategy has shown great promise in blocking HIV infection in a laboratory setting.27 Yet another approach is to block the cell’s own ACE2 receptor so there’s less of it for the virus to grab on to. As an analogy, this can be thought of as filling in a keyhole so that the key doesn’t work any more. The problem is that the lock (ACE2 receptor in this case) has a biological function within the body. Disrupting the ACE2 could have unintentional side effects. I mentioned that the virus needs the spike protein to be cut for infection to occur and this is done by host proteases. Removing the cellular proteases that SARS-CoV-2 manipulates to cut its spike protein is another way to design drugs. But here also, we need to be careful. Blocking proteases to prevent viral entry could also have unintentional side effects. Still, TMPRSS2 might be a reasonable drug target compared to furin. Thwarting this protease during ...