New Covid Pills Offer Hope as Omicron Looms

Drug developers have some good news as the world frets about the Omicron coronaviruses variant causing a surge of cases and weakened vaccines. Two new Covid-19 pills are coming soon, and are expected to work against all versions of the virus.

molnupiravir is a pill that reduces the risk of hospitalization and death from Covid-19 by 30 percent if taken within five days of the start of symptoms.

Pfizer has a pill that may perform even better. The drug was effective when taken within five days of the start of symptoms. The F.D.A. could authorize it by the end of the year.

Since the start of the Pandemic, scientists have hoped for convenient options like these: pills that could be prescribed by any doctor and picked up at a local drugstore.

The two pills may be just the beginning. Scientists say we will need an arsenal of drugs to deploy against new foes if the protection of existing vaccines is jeopardized by Omicron and other variant.

New drugs are being designed from scratch to target weak points in the coronaviruses. Some are testing whether pills work better together than alone.

Anthony Fauci, the government's top infectious disease expert, said thatviruses are wily creatures and you have to stay ahead of them. It would be foolish to think that you don't need any more drugs if you have a disease that has already killed 760,000 Americans.

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Pfizer has a new drug called Paxlovid, which is manufactured in Germany.

The early days of the Pandemic caused a scramble for Covid-19 pills. Researchers at pharmaceutical companies and academic labs looked at thousands of existing drugs to see if they could be used to fight the disease.

A success of this strategy would have led to an antiviral pill more quickly than trying to make a new drug. There was a wave of failures. When tested in animals and in clinical trials, the anti-virals that worked in Petri dishes failed.

Drugs that made it into trials were disappointing. Appili Therapeutics began a late-stage trial on more than 1,200 volunteers after receiving promising results in early trials of a flu drug called favipiravir. The company said that the pill did not speed up recovery from the disease.

Dr. Fauci said that not everything in research is a success.

A nonprofit company linked to the University of Georgia studied the new drug molnupiravir as a treatment for a little-known pathogen that is feared as a potential bioweapon. molnupiravir wreaks havoc when it encounters a virus's genes. New viruses can't replicate.

The drug reduced the risk of hospitalization and death by 50 percent, according to the initial results of the trial. The U.S. government has bought over 2 million courses of molnupiravir in order to curb the toll of Covid-19.

The drug's effectiveness dropped to 30 percent in the final analysis. The potential for the drug to cause genetic changes in people was discussed at a meeting of an F.D.A. advisory committee. The committee voted by a slim majority to recommend authorizing molnupiravir. The members of the committee who voted in favor of the drug expressed strong reservations.

Pfizer's drug is next in the spotlight. Pfizer researchers were looking for a drug that could fight the coronaviruses that caused the disease. They decided to build a molecule that could block the protease. The long molecule called a phosphatases act like scissors to help build new viruses.

The drug was lodged in the protease like a piece of gum. When given to rats, it proved to be effective against the disease.

The Pfizer could have launched a trial before the epidemic ended. The drug was pulled off the shelf after the Covid-19 outbreak.

They tinkered with the molecule to make it work as a pill. Pfizer's Paxlovid came out of clinical trials last month with terrific initial results: 85 percent effectiveness if taken within five days of the start of symptoms. The final analysis will determine if the number stays that high.

Pfizer applied for F.D.A. authorization of Paxlovid and reached a deal with the U.S. government to provide up to 10 million courses of the drug for $5.3 billion.

The F.D.A. will consider Paxlovid's potential side effects when reviewing the company's application. Paxlovid doesn't introduce any new genes so it won't raise the same red flags.

Sara Cherry, a virologist at the Perelman School of Medicine at the University of Pennsylvania, said that it is less likely to cause changes in our genes because it works through a different mechanism. She said that protease inhibitors have different liabilities.

Our own cells make proteases, which we use to cut down on our own proteins, which in turn allows them to perform new jobs. Some of the protease-inhibitor drugs can lock onto our proteases instead of the viruses that make them. The short course of pills needed to stop Covid-19 may reduce the risk from a drug like Paxlovid.

The advent of two drugs for Covid was exciting, especially as Omicron spread across the world, said Dr. Cherry. If Omicron reduces the effectiveness of vaccines, the pills will be very welcome, she said. The pills have no connection to the Omicron virus's outer spike protein, which is the cause of the worrisome mutations.

If we need to change the vaccines, that will definitely help us.

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Dr. Fauci was in 1985. Fauci, who oversaw the development of combination therapy for H.I.V., said that researchers will be able to quickly test combinations of pills to treat Covid-19 in clinical trials.

The first antiviral pills to show promise won't be the best. The first pill for H.I.V., a cancer drug called AZT, caused serious side effects and led to the evolution of AZT-resistant versions of the virus.

The pills that target H.I.V.'s proteases proved to be more effective than AZT. Combining the pills made them more effective. It was harder for the viruses to evolve resistance to the drug cocktails.

Dr. Cherry is working with her colleagues to see how well the drugs work against the coronaviruses. They found that combining molnupiravir and Paxlovid creates a more powerful impact than either drug has on its own.

The combined effect is called additivity. Researchers are looking for combinations that create synergy, an effect that is bigger than just adding the effects of two drugs together.

Dr. Mark Denison said synergy and additivity mean one plus one equals four. Those are possible.

Dr. Fauci oversaw the development of combination therapy for H.I.V. 30 years ago.

The Antiviral Program for Pandemics will have $3 billion to fund academic research centers developing new drugs. The first results from those studies could arrive in a year.

Each of the coronaviruses has a host of important genes that could be targets of a new drug. When a cell makes a new piece of the virus's RNA, a viralprotein called a helicase has to be untangled before it can be packaged into a new virus shell. The coronaviruses genes are in a mess because of drugs that block them.

The genetic material of the viruses is the focus of other researchers. When a coronaviruses injects its RNA into a human cell, the molecule moves into loops. The human cell can be manipulated by these structures.

In recent years, a number of drug developers have gone after these tangles. A chemist at Duke University said it was a small club.

Dr. Hargrove and her colleagues have modified various versions of a blood-pressure drug so that they can get to viral RNA. The researchers found three amilorides that grab the RNA of the disease. They found that the amilorides could reduce the production of viruses.

If any of these drugs work, they could open the way for even more powerful cocktails.

Denison said that he wanted to hit the virus from every side. You want to cut the tires and ruin the brakes.

Researchers at the Walter Reed Army Institute of Research are trying to develop a pill that will work against all coronaviruses. They are looking for targets that are common to all coronaviruses. They used a computer to screen 41 million compounds for drugs at the start of the Pandemic last year.

They ran experiments on 800 candidates and only a few of them were the best.

Brandon Pybus, one of the Walter Reed researchers, said that using artificial intelligence shaved many years off the project. The team will not be able to move as fast as Pfizer or Merck because they are making a drug from scratch. He said it could take a few years if resources permit.

Dr. Fauci and his colleagues will use the same strategy to search for drugs that work on other viral families, such as togaviruses, which cause diseases like chikungunya and West Nile fever.

Dr. Fauci said that he has a lot of confidence in the investigators' ability to come up with crazy ideas that turn out to be really, really good.