What is Molnupiravir?

Molnupiravir is an investigational, orally administered form of a potent ribonucleoside analogue that inhibits the replication of SARS-CoV-2, the causative agent of COVID-19. Molnupiravir has been shown to be active in several preclinical models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission. Additionally, pre-clinical and clinical data have shown molnupiravir to be active against the most common SARS-CoV-2 variants.

Why is it creating such an uproar?

While there are a number of treatments for COVID-19 on the market, many of them are expensive, difficult to administer, not widely available, or only marginally effective. Meanwhile, treatments that have little evidence behind them, like the antiparasitic drug ivermectin and the anti-malaria drug hydroxychloroquine, have gained traction in some circles. Molnupiravir, originally developed to treat influenza, could solve many of these challenges. It’s administered as a twice-a-day pill for five days, compared to other COVID-19 treatments that require expensive intravenous transfusions, such as monoclonal antibodies and convalescent plasma. The antiviral drug remdesivir, currently the only drug with full US Food and Drug Administration (FDA) approval to treat COVID-19, also has to be delivered into the bloodstream.

How does it work?

Molnupiravir works a lot like the antiviral drug remdesivir. The SARS-CoV-2 virus, which causes COVID-19, makes copies of itself by encoding instructions on RNA, which is made up of “base” molecules identified by the letters A, C, U, and G. While remdesivir imitates A (adenosine), molnupiravir can mimic U (uracil) or C (cytosine). When the virus incorporates remdesivir into its RNA, the drug causes its reproductive cycle to stall. Molnupiravir works a little differently, causing genetic mutations that hamper the virus. Crucially, these drugs can fool the virus, but they don’t fool human cells, so they have a targeted effect and for the most part, leave the human cells alone. Merck didn’t note any specific side effects from molnupiravir in its press release and said the rate of complications was similar between the placebo group and the treatment group in the clinical trial.

Is it a game changer?

The Merck drug, known as molnupiravir, reduced the risk of hospitalisation or death by 50 per cent in an interim analysis of a late-stage clinical trial. However, we should treat this carefully. We have limited study information so far although it is very encouraging.

Why is it encouraging?

This is due to the decision of the Data Safety and Monitoring Board (DSMB) in the US, a group of outside experts not involved in the trial, who review updated data regularly with no idea which people are receiving the drug and which are receiving placebo. They saw a strong enough difference to stop the trial before completion: only 775 people were randomised, less than half of the 1,850 planned participants. Thankfully, the group with the better outcome turned out to be those on molnupiravir, not placebo. Of those 775 participants, all had at least one co-morbid condition placing them at higher risk for progression to severe disease; 385 received the active drug and saw their rate of hospitalisation or death reduce from the 14.1 per cent (seen in the placebo group) to 7.3 per cent, according to the study. Furthermore, the company reported that the new drug had fewer side effects than placebo. This is good news for sure. But more information is needed. For example, information on teens and younger children, a population that could possibly benefit greatly, given the lack of authorised vaccines for 11-year-old and younger kids. Another thing that we should also remember, the trials were done at early stages of COVID-19 infection, within five days of COVID-19 symptoms. Does it work at late stages? During severe symptoms? Category 4/5 patients? Remains to be seen!

How can this help fight against COVID19?

Although vaccination remains the most important shield against COVID-19, at the same time, many other countries still don’t have access to enough vaccines. The unvaccinated continue to make up the majority of hospitalisations and deaths around the world. Treatments for COVID-19, therefore, remain a vital component of the response to the pandemic. But developing new drugs to treat an illness is expensive and time-consuming, which is why researchers have been eager to find off-the-shelf therapies that have already been deemed safe to use against other ailments.

Some have proven fruitful, like the corticosteroid dexamethasone. Scientists have also seen promise in the antidepressant drug fluvoxamine as a therapy. New drugs like molnupiravir require more testing and review, but they offer the possibility of a stronger, more targeted approach. A drug like molnupiravir could be especially useful because it is administered in the early stages of the disease. Since it’s just a pill, it may spare the patient a trip to a clinic for a transfusion for treatments like monoclonal antibodies. That reduces the chances of an infected patient transmitting the virus to medical staff, and it averts potential complications associated with transfusions.

If the results hold up to scientific scrutiny (further review on efficacy and data on a larger population), this is very big news indeed. Effective pills given to outpatients could make a large difference for several distinct groups: for people with mild illness, it could prevent progression to more severe, even life-threatening illness, as the study apparently shows; provide an alternative approach to prevent severe disease in people who are against vaccinations and vaccine-non-responders (those with severely weakened immune systems); and potentially protect those with recent close exposure to an active case.

Should we ditch vaccines?

This is very important issue to understand! Vaccines remain the ultimate shield for our fight against the pandemic. Vaccines offers long term, robust and durable protection via immunological memory against COVID-19 before the real infection itself, training our body to be ever ready to fight this disease something an antiviral pill could not provide. Vaccination and booster shots (for select individuals) should remain the long term priority for governments worldwide in the fight against this pandemic. Rather than ditching vaccines, antiviral strategies such as this (using Molnupiravir for example) should be added as part of our portfolio to fight COVID-19 and future pandemics to give a “synergistic” effect that will have a better outcome.

Since the current trial data was done only in unvaccinated individuals, it remains to be seen, how the drug will react in vaccinated individuals suffering from breakthrough infections (exhibiting severe symptoms). Extremely promising I believe!!!