Since the outbreak of the COVID pandemic all attention has been focused on vaccines to contain the disease. That is a first step towards control. But eventually, we need to have a cure. COVID medicine is coming.
Despite the effectiveness of vaccines, we still need drugs to treat COVID. Even people who have been double vaccinated stand a small chance of being infected and ending up moderately or even severely ill. There are drugs, but they have to be given in hospital. That may change soon, if we are to believe the signs that COVID medicine is on the way.
One promising drug that could improve things is molnupiravir, an antiviral that’s moving into the final stages of testing in humans. Researchers are hoping it can be used both to treat and prevent COVID. Importantly, it can be taken as a pill – meaning people wouldn’t need to be hospitalised to receive it.
This drug reduces the ability of SARS-CoV-2, the virus that causes COVID, to replicate. It works by mimicking one of the building blocks of the virus’s genetic material. When the virus reproduces, it builds a new copy of its RNA, and the drug ends up being incorporated into it.
When the virus then reproduces, the molnupiravir causes mutations to accumulate in the virus’s RNA, which increase every time it replicates. Eventually, this causes an “error catastrophe”, where excessive mutations stop the virus from being able to reproduce altogether, and it dies off.
How well does COVID medicine work?
So far, a small trial has looked at the effects of molnupiravir in 202 COVID patients (not in hospital) who had started having symptoms. Participants were randomly allocated to receive molnupiravir or a placebo, with different doses of the antiviral being tested.
The trial’s results have been published as a preprint, meaning they are yet to be formally reviewed by other scientists. Still, the trial showed that after three days of treatment, infectious SARS-CoV-2 virus was found significantly less often in participants taking 800mg of molnupiravir (2%) compared to those taking a placebo (17%).
By day five, the virus was not detected in any participants receiving 400mg or 800mg of molnupiravir, but was still found in 11% of those taking a placebo. The trial, therefore, suggests that molnupiravir can reduce and eliminate infectious SARS-CoV-2 in patients with mild COVID. Indeed, it’s the fact that molnupiravir speeds up the clearance of the virus that suggests it could be useful not just for treating COVID but also lessening the chance of it spreading.
But to know just how useful it will be, we need to see what happens in further trials. Molnupiravir is currently also being assessed in newly hospitalised patients, with this study aiming to find out if early molnupiravir treatment can reduce the time it takes for patients with severe COVID to clear the virus. No results have been disclosed so far.
A larger trial, with 1,850 participants, is now looking to see if molnupiravir is better than a placebo at preventing serious disease and death in non-hospitalised adults with COVID. And a phase 3 trial (the final stage of human testing) is now recruiting participants – across 17 different countries – to see whether early molnupiravir treatment of COVID-positive people prevents others living in the same household from getting infected. Previous research has already shown molnupiravir can stop SARS-CoV-2 spreading in this manner among ferrets.
If it performs well in these trials, molnupiravir’s impact could be huge. Given the severity of illness that can be caused by SARS-CoV-2, an effective antiviral would be a valuable weapon to have in the clinical armoury – particularly if molnupiravir continues to be as fast acting as it has so far in testing. Patients suffering from COVID can become very sick very quickly.
The fact that it is taken orally is also potentially very helpful, as this would make it easy to use in the early stages of infection, as it could be self-administered outside of hospital. Also, molnupiravir can be produced in large quantities and doesn’t require cold transportation. Vaccines and physical measures to control the spread of the virus would still be the primary tactics for managing COVID, but this drug could complement both.
Pfizer and Ritonavir
Two others include a candidate from Pfizer, known as PF-07321332. Pfizer has dosed the first subject in Phase II/III clinical trial of its experimental oral antiviral drug in non-hospitalised patients who have symptoms but are at low risk of progression to severe disease.
A protease inhibitor, PF-07321332 is meant to hinder the activity of the main protease enzyme that the SARS-CoV-2 virus requires for replication. When given in combination with a low dose of ritonavir, the antiviral’s metabolism or breakdown is expected to slow down, allowing it to stay longer in the body at higher concentrations.
This long-term action inside the body could facilitate a continuous fight against the virus, Pfizer said. Previously, ritonavir was administered along with other antivirals for a similar slowing of metabolism.
The latest double-blind Phase II/III trial will randomise nearly 1,140 subjects to receive either oral PF07321332 plus ritonavir or placebo every 12 hours over five days.
The trial is expected to complete next year.
Roche and Atea
A third candidate is AT-527, an antiviral produced by Roche and Atea Pharmaceuticals. AT-527 is an oral direct-acting antiviral agent developed from Atea’s nucleotide prodrug platform. The antiviral drug blocks viral RNA polymerase, which is needed for viral replication. The asset is being investigated in multiple trials against COVID-19. It is being studied in hospitalized settings and outpatient settings and for the treatment of long-haul COVID-19.
