How the Merck and Pfizer Pills Work? – Community News
Covid-19

How the Merck and Pfizer Pills Work?

Covid-19 may soon be treatable with a pill.

In the past six weeks, two drug manufacturers have announced promising clinical research results for their experimental oral antiviral pills and their data will soon be evaluated by the Food and Drug Administration.

The first drug comes from Merck, which partnered with Ridgeback Biotherapeutics on a drug called molnupiravir, an antiviral drug originally developed to treat flu viruses. An FDA advisory committee will meet on Nov. 30 to discuss the companies’ request for emergency use approval. And last week, Pfizer announced the results of its clinical trial of the antiviral Paxlovid and said it would submit its data to the FDA in the coming weeks.

Molnupiravir and Paxlovid, which are designed to be administered as pills, have proven remarkably successful in placebo-controlled clinical trials in preventing hospitalization and death from Covid-19. Experts hope the authorization of the drugs will be an important step towards ending the Covid-19 pandemic.

So how do the antiviral drugs work?

The coronavirus is wreaking havoc on the body by putting itself in cells and hijacking their machines to make copies of itself. The copies then burst out of the cells and invade other cells and spread throughout the body.

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Molnupiravir and Paxlovid are both intended to prevent the coronavirus from multiplying, but they use slightly different methods.

Molnupiravir, a type of antiviral medicine called a polymerase inhibitor, works by preventing the virus’s genetic material from replicating accurately. It fools the enzyme (called a polymerase) that is responsible for replicating the virus’s RNA so that it inserts errors or mutations. The mutations are then replicated over and over until there are so many mutations that the virus can no longer survive.

The so-called failure catastrophe method is effective, said Katherine Seley-Radtke, a medical chemist at the University of Maryland, Baltimore County, who specializes in antiviral drug development.

But “it’s also a bit risky, because it can also hit human host enzymes,” she said. Some research suggests that medicines similar to molnupiravir may have effects on other enzymes in the body when given for long periods of time (molnupiravir is taken for five days). “But it still causes concern,” she added.

Pfizer’s drug, Paxlovid, takes a different approach.

The drug consists of two components: an experimental molecule called PF-07321332 and an existing drug called ritonavir. Both are protease inhibitors, meaning they block another enzyme (called a protease) that breaks down long strands of non-functional viral proteins into smaller, functional proteins. PF-07321332 is the star of the show in the drug duo, which works on the virus itself, while ritonavir prevents other enzymes from destroying PF-07321332. Ritonavir plays the same defensive role in cocktails of antiviral drugs that treat HIV.

For both drugs, it is important to start treatment early. In the clinical studies, Merck and Pfizer started treatments within five days of the onset of symptoms.

“These drugs can be administered at any stage of infection based on their mechanism of action,” said Fenyong Liu, a virologist at the University of California, Berkeley. However, they will be more effective if given in the early stages of infection, he added, “because more serious complications and damage from infection are always associated with later stages.”

That’s because the longer the virus has to make more copies of itself, the more it will spread and cause problems, Seley-Radtke said. If the virus is stopped early, the consequences will be less severe, she said.

The clinical trials for both treatments reported no adverse side effects different from those of the placebo, which experts say is promising.

While there’s probably room to improve the drugs, Liu said, “I think they’re really the best thing we can do right now.” Both were initially developed for other purposes but have been repurposed for Covid-19 due to urgency, he said. The potency and safety profile of the treatments is likely to improve as there will be second and third generations of the drugs by making minor changes to their chemical makeup, he said.

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Seley-Radtke is hopeful that the drugs are as safe as the companies suggest, but she noted that Pfizer hasn’t released much data on its new drug, making it difficult to confirm its safety at this time.

A major advantage of the new drugs over existing Covid-19 drugs is that they come in pill form rather than as intravenous drugs. For example, the antiviral drug remdesivir is a polymerase inhibitor that works in a similar way to molnupiravir and has been shown to be effective against Covid-19, but it can only be given by IV. Remdesivir, which was approved by the FDA in October 2020, is being used to treat hospitalized patients.

Drugs for Covid-19 treatment should be considered for global use, Liu said, and an IV drug isn’t practical in many parts of the world. “The availability of the treatment is very, very important, just as important as the efficacy of the drug itself,” he said.

And hopefully Covid-19 drugs in the form of pills will not only help people heal, but also stop the virus from spreading. “About 80 percent of the people [with Covid-19] don’t have to go to the hospital,” Seley-Radtke said. “They could be treated very early and knock out that virus immediately,” stopping it from spreading any further. “That’s going to be huge.”

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