Chemists at Pfizer’s research facility in Connecticut dusted off some ideas the company had developed during the SARS outbreak in 2003. Even back then, an obvious line of attack had been to block a well-understood component of the virus life cycle involving a key protease, a protein that orchestrates how the virus copies itself. Find a chemical that is able to stick tightly enough to that protein, and it would stop the virus from replicating in the body, lessening the chances that a patient would become seriously ill.
Right away, researchers got a lucky break. When Pfizer checked, it found that none of the thousands of proteins in the human body shared the same bit of molecular structure they planned to interfere with in SARS-CoV-2. That meant they could hit the virus hard and not expect any major side effects. Nature had provided the scientists with a big bull’s-eye. “This is the most solid biological target I have ever worked on,” says Pfizer chemist Dafydd Owen.
Crucially, the protease is, in the jargon of biologists, a “highly conserved” molecule. That means that even as the virus evolves, this part rarely changes. So while the coronavirus has been mutating quickly to evade vaccines, so far it looks as though Paxlovid will work just as well against any variant—whether it’s omicron or whatever comes next.
In fact, laboratory tests run by Pfizer suggest Paxlovid will work against all coronaviruses, maybe even one still lurking in a bat cave somewhere. If so, it means the company has hit on a potential defense against the next outbreak, too. “It has the potential to be a pan-coronavirus agent and stockpiled against future pandemics,” says Owen, the Pfizer chemist. “But it’s here for this pandemic, because we did it super fast.”