Pfizer’s COVID pill benefited from SARS research: Shots

Scientists at Pfizer’s research and development labs in Groton, Connecticut, have been working on the COVID-19 pill called Paxlovid.

Stew Milne / AP

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Stew Milne / AP

Scientists at Pfizer’s research and development labs in Groton, Connecticut, have been working on the COVID-19 pill called Paxlovid.

Stew Milne / AP

Two new drugs are awaiting approval from the Food and Drug Administration to treat patients with COVID-19, and both may be effective against the omicron variant.

One is made by Merck, the other by Pfizer.

The drug Merck has been in development for years. At the start of the pandemic, Pfizer’s drug did not exist. The story of its development is another example of how COVID-19 has sped up the process of drug and vaccine development.

Pfizer wasn’t exactly starting from scratch. Mikael Dolsten, chief scientific officer of Pfizer, said that during the SARS outbreak in 2003, company scientists started looking for ways to combat this coronavirus.

In particular, they looked for proteins that are crucial for the virus to replicate once it has infected someone.

Pfizer Focuses on Replication Needs of Protein Viruses

A viral protein they focused on is called a protease. “We have learned that protease is a key regulator for the virus to release its machinery and hijack human cells,” explains Dolsten.

Scientists at Pfizer believed that if they could find a compound that disrupted protease, it would essentially stop the virus in its tracks.

This research ended when the SARS epidemic of 2003 passed. No disease, no market for a drug.

But Dolsten says the knowledge gained convinced them that a protease inhibitor would work to lock up the coronavirus causing COVID-19.

They created computer models of the viral protease protein and assembled drug candidates that could block it.

“In fact, we had to design and synthesize some 600 unique chemical compounds,” he says.

An old medicine helps the new medicine to work better

It was just the beginning. They had to test each compound to see how well it was preventing the virus from infecting cells in the lab. Then they had to determine if it would do the same in animals infected with the coronavirus. They also had to find a candidate who would stay in someone’s body long enough to have the desired antiviral effect. And they wanted to do it all quickly.

“We put in a very tight timeline where we made it all happen over four months to get to the optimal medicine,” Dolsten said.

Ultimately, the drug developers had a candidate they thought would work. They mixed it in a pill with an old medicine called ritonavir which made the protease inhibitor work longer.

Last July, Pfizer launched a study of people infected with the coronavirus who were at high risk of developing severe COVID. Half received the drug, called Paxlovid, within three to five days of symptom onset, half received a placebo.

Dolsten says the study was ended prematurely because the drug seemed to be working. He says there has been an almost 90% reduction in hospitalizations among people taking the new drug, “and 100% protection against death.”

A similar analysis for the drug Merck found that it reduced the risk of hospitalization or death by 50%. In a subsequent analysis presented to the FDA, however, the risk reduction fell to 30%.

A good thing about these drugs is that they are pills, they can be taken at home, unlike some current therapies which require an infusion.

Because Pfizer’s pill is unaffected by changes in spike protein, Dolsten says he expects the new drug to work equally well against any variant of the coronavirus, including omicron.

Although Pfizer has yet to release details of its study, the researchers seem impressed.

“I think this drug as well as the drug from Merck are both very promising antivirals which, as we predicted at the start of this pandemic, work when given early in the infectious course,” says Stanley Perlman, microbiologist at the University of Iowa, where he has worked on coronaviruses for decades.

Perlman adds that the key to preventing damage from a coronavirus infection is to prevent it from replicating and spreading throughout someone’s body.

Protease is not the only viral protein that could lead to viable treatment.

“I think there are several other targets in the way the virus reproduces itself,” says Perlman. “But the most important thing for everyone to think about is that almost all of them need to be given very soon after infection to really play a role in preventing progression to more serious disease.”

And since it looks like we will be living with COVID-19 for a while, there is an incentive for drugmakers to develop other types of drugs to treat the disease.