New antiviral drugs mark a major turning point in the covid-19 pandemic

THE LAST The news of the fight against covid-19 is encouraging. Two new antiviral drugs have been considered so effective that clinical trials were terminated early. Data from these trials have not yet been published. However, regulators are quick to assess the general use of the drugs. They will fill a large gap in the toolkit doctors use to fight the virus, and may well help end the global pandemic.

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The new drugs are molnupiravir (Lagevrio), developed by Merck, a pharmaceutical company that collaborates with Ridgeback Biotherapeutics, a biotechnology company, and Paxlovid, which was developed by Pfizer. All three are American companies. Those who are most exposed to the serious effects of covid are far less likely to be hospitalized, or die, if they take a cure with one of these pills within the five days after the symptoms first appear.

Merck said in October that molnupiravir reduced the risk of hospitalization or death by about half, when given to patients with a single risk factor for covid, such as obesity or heart disease. Regulators in America, Europe and the World Health Organization are evaluating the drug. The UK has approved it and will start using the treatment next month. On November 5, Pfizer said their pill reduced the risk of hospitalization or death by 89% if taken within three days. (In fact, during the trial, no patient died at all when taking Paxlovid within five days of symptoms.)

Molnupiravir is what is known as a prodrug, which means that it is converted to its active form when it enters the cells. Once there, it is incorporated into the genetic material of the virus, thereby interfering with its ability to replicate. Errors accumulate in the genetic material of the virus, a process known as “error disaster”. Animal experiments have raised concerns that the drug may pose a risk to unborn children, therefore the UK Government has advised against its use during pregnancy or lactation. Other regulators may issue similar warnings.

Paxlovid is actually a combination of two drugs: an existing one called ritonavir, which is co-administered with a new protease inhibitor known asPF-07321332. The protease inhibitor was designed to bind and block the protease enzymes that SARS-COV-2 uses to replicate. Ritonavir prevents the protease inhibitor from being broken down too quickly in the body.

Molnupiravir and Paxlovid are also known as “small molecule” drugs. These are molecules that are easy to make. Both companies say that the price of the drugs will vary according to the wealth of the nation that buys them. This is likely to mean that rich countries will pay $ 700 for a five-day course with pills, while the poor can pay around $ 20, and perhaps less as production costs fall.

Although both companies have stated that they intend to make these drugs widely available worldwide, Merck already has an advantage. It has signed a number of licenses that allow other manufacturers to produce the drug, and it has reserved 3 million doses for low- and middle-income countries. This is to ensure that rich countries do not monopolize the supply of the new medicines as they have done for vaccines. Merck expects to make 10 million doses this year, and 20 million next year. Generic manufacturers will make many more. Pfizer, which has not yet received any regulatory approvals, expects 180,000 packets of pills to be produced by the end of this year, and 21 million in the first half of 2022.

These drugs signal another major turning point in the pandemic (the first is vaccines). The growing number of cases across Europe suggests that there will be a strong demand for such medicines to keep people out of hospitals. While patients wait for their arrival, it is also possible that doctors may consider the use of fluvoxamine, an antidepressant drug that also appears to reduce the risk of covid.

As the new treatments are launched for use, there will be concern among some researchers and doctors that the virus is developing resistance, especially if patients do not complete the course. Keeping one step ahead of SARS-COV-2 will require planning for such an eventuality. This means deriving which antiviral drugs can be given in combinations to create a therapy that the virus will struggle to defeat.

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This article appeared in the section Science and Technology in the print edition under the heading “Pills with promise”

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