Two years into a pandemic that has tested every tool humanity has, two pills have arrived that aim not to prevent infection but to interrupt the virus once it has taken hold. The UK's regulator has approved molnupiravir, and Pfizer's paxlovid has shown striking early results that still await the scrutiny of other scientists. Both work by different routes, and both offer a way to protect the most vulnerable at home, though their fullest promise depends on reaching people early enough and on using them wisely.
How Merck's molnupiravir and Pfizer's paxlovid work, and how they could be used against COVID-19
Covid patients at risk of severe disease face hospitalisation or death, which these oral antivirals aim to reduce.
By the time someone is raced to hospital gasping for oxygen, it may be too late
Mark
Both drugs stop the virus copying itself. Why does it matter that they do it differently?
Mimi
Because drugs with different mechanisms are much more likely to work well in combination. One corrupts the virus's RNA, the other jams an enzyme it needs.
Mark
And the practical advantage over other treatments?
Mimi
They're pills. Monoclonal antibodies need an infusion or injection, but these can be taken at home, early in the illness.
Luke
Early is doing a lot of work there. What are the actual windows?
Mimi
Molnupiravir within five days of symptoms starting, ideally right after a positive test. Paxlovid seems to help within three to five days.
Luke
And the 89% figure for paxlovid? Set that beside molnupiravir's halving.
Mimi
Careful, it's interim data and hasn't been peer reviewed. Regulators haven't authorised it, and it's unlikely before next year.
Luke
So the two numbers shouldn't be treated as a head-to-head result.
Mimi
Right, the article doesn't claim that. It only says they came from different trials.
Mark
Who gets the drugs, then?
Mimi
Not everyone. With around 40,000 positive tests a day in the UK, supply is short and most wouldn't benefit, so the aim is the vulnerable, such as older people or those with weak immune systems.
Luke
Whether the systems exist to find those people fast enough is still unanswered.
O Pulso
- The UK regulator has approved molnupiravir, which halved the chance of hospitalisation or death among at-risk adults with mild to moderate Covid.
- Pfizer's paxlovid reported an 89% risk reduction in interim data, but those results have not yet been reviewed by independent scientists.
- Doses are too scarce to cover the roughly 40,000 daily UK positive tests, so guidelines must steer the drugs toward the most vulnerable.
- Timing is tight: molnupiravir must start within five days of symptoms, and paxlovid within three to five, before the virus causes serious damage.
- Paxlovid is unlikely to reach patients before next year, leaving molnupiravir alone in use while resistance concerns demand careful stewardship.
Two years into a pandemic that has tested every tool humanity has, two pills have arrived that aim not to prevent infection but to interrupt the virus once it has taken hold. The UK's regulator has approved molnupiravir, and Pfizer's paxlovid has shown striking early results that still await the scrutiny of other scientists. Both work by different routes, and both offer a way to protect the most vulnerable at home, though their fullest promise depends on reaching people early enough and on using them wisely.
Twenty months into the pandemic, two oral antivirals now stand at the threshold of wider use. Earlier this month the UK medicines regulator approved molnupiravir, developed by Merck and Ridgeback Therapeutics, which among at-risk adults with mild to moderate Covid halved the chances of hospitalisation or death. Pfizer has since released interim trial results for its own drug, paxlovid, suggesting an 89% reduction in risk among the most vulnerable.
The two drugs attack the virus in different ways, as Alexander Edwards of the University of Reading explains. Molnupiravir slips a counterfeit building block into the virus's genetic material, so that errors accumulate until the virus can no longer copy itself. Paxlovid binds to a protease, an enzyme the virus needs, and halts it. Drugs with different mechanisms are more useful together, and the protease paxlovid targets is shared by most coronaviruses, offering hope against future relatives of Sars or Mers.
The caveats are real. Pfizer's figures have not been checked by other scientists, and paxlovid must pass regulatory review, likely not reaching patients until next year. Both pills are taken at home, which matters because timing is everything: they work best early, before a patient deteriorates and needs hospital oxygen. With roughly 40,000 positive tests a day in the UK, supply cannot cover everyone, so guidelines focused on older people and those with weakened immunity will be essential. Antivirals may also support people who respond poorly to vaccines, though careful use will be needed to guard against resistance.
Twenty months into the pandemic, two pills now exist that are meant to blunt the coronavirus. Earlier this month the UK medicines regulator approved molnupiravir, the antiviral developed by Merck and Ridgeback Therapeutics. Among adults with mild to moderate Covid who were at risk of serious disease, it halved the chances of being hospitalised or dying. Pfizer has since released trial results for its own antiviral, paxlovid, which suggest an 89% cut in the risk of hospitalisation or death among those most vulnerable.
The two drugs attack the virus differently, according to Alexander Edwards, associate professor in biomedical technology at the University of Reading, who set out the comparison in an article first published by The Conversation. Molnupiravir mimics a building block of the virus's genetic material. When the virus copies itself, the imposter is written into its RNA and introduces errors. Once enough pile up, an "error catastrophe" stops the virus reproducing. The drug is named after Mjölnir, the hammer of the god Thor.
Paxlovid also halts replication, but by binding to a protease, an enzyme the coronavirus needs in order to reproduce, and stopping it working. Edwards calls it tremendous news that two different classes of antiviral have succeeded, since drugs that work in different ways are far more likely to be useful in combination than two that work the same way.
Both could also reach beyond Covid. Molnupiravir and similar drugs may work against other RNA viruses, and the drug began life as a candidate for influenza and respiratory syncytial virus. The protease paxlovid blocks is found in most coronaviruses, which raises the hope of never again meeting a new relative of Sars or Mers with no medicines at all.
The caveats are real. Pfizer's figures are interim and have not yet been reviewed by other scientists, and regulators must scrutinise them before paxlovid is authorised. Even if all goes well, it is unlikely to be available until next year, so for now only molnupiravir will be used.
Both drugs are taken orally, unlike monoclonal antibodies, which need an infusion or injection, so patients can take them at home. That matters because timing is hard. Molnupiravir should be taken as soon as possible after a positive test, and within five days of symptoms starting. Paxlovid appears to help when given within three to five days of symptom onset. By the time someone has deteriorated and is rushed to hospital short of oxygen, it may be too late, because the virus may already have done serious damage.
Knowing whom to treat is the other problem. There are not enough doses for everyone with a respiratory infection, or even for the roughly 40,000 people testing positive in the UK each day, and most of them would not benefit. Edwards argues that guidelines, based on what is already known about who is most vulnerable, such as older people or those with weak immune systems, could direct the drugs where they are needed, which makes early detection of infection in those groups paramount.
Vaccines have been hugely successful against severe disease, but they are not protective every time, and waning protection appears to be a problem, so some fully vaccinated people still get severe Covid. Some people, because of certain conditions or medicines, do not respond well to vaccination at all. Antivirals could back up the vaccine programme for them. Edwards also expects a burst of investment in antiviral science, and warns about resistance: molnupiravir's error catastrophe is hard for the virus to escape, but careful use will be essential, as with antibiotics.
Citações Notáveis
Developing these drugs isn't the end of the story; systems must be in place to use them most effectively.— Alexander Edwards, University of Reading
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