This strategy was a long shot, but a success would have led to an antiviral pill more quickly than trying to make an entirely new drug. What followed was a brutal wave of failures. Antivirals that worked in Petri dishes failed when tested in animals, and those that worked in animals failed in clinical trials.

Even drugs that made it into clinical trials often proved disappointing. A flu drug called favipiravir delivered promising results in early trials, leading Canada-based Appili Therapeutics to begin a late-stage trial on more than 1,200 volunteers. But on Nov. 12, the company announced that the pill did not speed up recovery from the disease.

“Not everything in research is a big success,” Dr. Fauci said.

Merck’s new drug, molnupiravir, was studied in 2019 by a nonprofit company linked with Emory University as a treatment for Venezuelan equine encephalitis virus — a little-known pathogen feared as a potential bioweapon. When molnupiravir encounters a virus’s genes, it wreaks havoc, leading to a batch of new mutations. New viruses are often left unable to replicate.

In October, Merck announced the initial results of its molnupiravir trial: The drug reduced the risk of hospitalization and death by about 50 percent. Eager to curb the toll of Covid-19, the U.S. government has bought approximately 3.1 million courses of molnupiravir for about $2.2 billion.

But in the final analysis of the trial, the drug’s effectiveness dropped to 30 percent. At a Nov. 30 meeting of an F.D.A. advisory committee, experts discussed the potential for the drug to cause mutations not just in viruses, but in people’s own DNA. The committee voted to recommend authorizing molnupiravir, but only by a slim majority. And even the committee members who voted in favor of the drug expressed strong reservations, given the potential side effects.

Now, Pfizer’s drug is next to enter the spotlight. Its origins reach back nearly two decades, to when Pfizer researchers were searching for a drug that could fight the coronavirus that caused SARS. They decided to build a molecule that could block an essential viral protein, known as a protease. Proteases act like molecular scissors, cutting long molecules into pieces that help build new viruses.

The drug, originally called PF-00835231, lodged in the protease like a piece of gum crammed between scissor blades. PF-00835231 proved effective against SARS when given intravenously to rats.



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