How powerful is the Covid-19 treatment drug Molnupiravir, named after Thor's hammer Mjölnir?

The emergence of a simple oral drug like molnupiravir would fill all the gaps left by the above treatments. It has proven effective, is easy to deploy on a large scale, and is easy to store and transport around the world because it is a capsule rather than an injection.

So we finally have an oral drug specifically for Covid-19 . Last Friday, the US pharmaceutical company Merck said it had completed phase III clinical trials of an antiviral drug for SARS-CoV-2 called molnupiravir - named after the hammer of the god of thunder Thor Mjölnir.

Trial results showed that molnupiravir was more than 50% effective in preventing hospitalization and death from Covid-19 infection in people with the risk of severe progression. Notably, the drug can fight all strains of the virus , from Delta, Gamma to the latest variant Mu.

The SARS-CoV-2 antiviral drug is called molnupiravir.

'We predicted that from our laboratory studies, and now this [phase III clinical trial] result confirms it. You know, this drug is named after Thor's hammer, and it will be a hammer against SARS-CoV-2 regardless of how they mutate, ' said Dean Li, head of R&D at Merck.

Based on the very positive results of phase III clinical trials, Merck and molnupiravir's manufacturer Ridgeback Biotherapeutics are applying for emergency use authorization to the US Food and Drug Administration (FDA), with the hope of bringing this weapon into the fight against Covid-19 as soon as possible.

A thunderbolt to the SARS-CoV-2 virus

Molnupiravir is a small molecule that targets a key enzyme in the SARS-CoV-2 virus called RNA-dependent RNA polymerase (RdRp). This long name can be shortened to replication enzyme , because it catalyzes the copying of SARS-CoV-2 RNA, which gives the virus the ability to rapidly reproduce and multiply once it enters a patient's lungs.

Once in the body, the molnupiravir molecule finds the virus and delivers a devastating blow to its RNA polymerase. This thunderbolt comes from the fact that molnupiravir can tamper with a nucleotide base called cytidine (C).

Once it binds to the virus's RdRp enzyme, molnupiravir halts its replication cycle, creating genetic mutations that kill or inactivate the SARS-CoV-2 virus. Researchers call this a " viral catastrophe ," because once the rate of gene mutations exceeds a certain number of replication errors, the virus cannot survive and cause disease.

Molnupiravir's mechanism of action is therefore more potent than the currently used drug remdesivir. While remdesivir also uses a similar mechanism of replacing the Adenosine (A) nucleotide in the virus's replication machinery, it only has the ability to prevent the virus from replicating without causing mutations to kill them like what molnupiravir does.

The molnuporavir hammer is a thunderous blow to the replication enzyme (RdRp) of the SARS-CoV-2 virus.

Before the Covid-19 pandemic, Merck was researching molnuporavir as a drug to fight the influenza virus. However, in March 2020, when Covid-19 peaked and became a global pandemic, they found themselves needing to pivot to create an antiviral drug against SARS-CoV-2 based on the principle of attacking that replication enzyme.

There have been concerns that these nucleoside decoy drugs could also cause problems with human cell replication enzymes, and for this reason, they have not been tested or approved for use in pregnant women.

However, all animal and clinical trials to date have shown that molnuporavir is highly safe. Scientists at Merck said the rates of side effects were similar in the drug and placebo groups, at 11% and 12%, respectively.

Phase III clinical trial results are extremely promising

Before using it for SARS-CoV-2, Merck said it had tested molnuporavir on other coronaviruses, specifically SARS-CoV and MERS-CoV. It showed that molnupiravir improved lung function, reduced viral load, and improved infection-induced weight loss in laboratory animals.

Other preclinical studies continue to confirm that molnupiravir can kill SARS-CoV-2-infected cells from the human respiratory tract.

In its latest phase III clinical trial involving 775 Covid-19 patients, Merck recruited adults at high risk of severe illness and death to take molnupiravir. They had to have at least one risk factor for poor outcomes, such as obesity, diabetes, heart disease or being 60 or older.

Half of the volunteers will be given two molnupiravir tablets a day, 12 hours apart, for five days. The other half will be given a placebo and standard care like other Covid-19 patients.

Only 7.3% of patients taking molnupiravir were hospitalized or died, compared with 14.1% in the placebo group.

After 29 days of follow-up, 53 of the 377 participants who received the placebo were hospitalized for severe Covid-19, and eight of them died. In contrast, only 28 of the 385 people who received the real molnupiravir were hospitalized, and none died.

In other words, only 7.3% of patients taking molnupiravir were hospitalized or died compared to 14.1% in the placebo group, which is the basis for Merck to claim that its Covid-19 drug is 50% more effective.

The manufacturer noted that it also took samples from patients participating in the trial for genetic sequencing, which identified up to 40% of patients infected with the variant. This means that molnupiravir is likely to work against different Covid-19 variants, including Delta, Gamma and Mu.

"Bring me COVID"

Although there are already a number of treatments for Covid-19, the downside of all of these methods is that they are difficult to use, expensive , and not very effective.

The first drugs used in the pandemic, ivermectin and hydroxychloroquine, were once considered hopeful but ultimately proved ineffective. Next, the method of infusing convalescent plasma or monoclonal antibodies is more effective, but extremely difficult to implement and cannot be deployed on a large scale. Because it requires very complicated steps, from collecting blood, filtering serum, producing antibodies, storing and then infusing into new patients.

The most common treatment for Covid-19 right now is remdesivir, an intravenous drug. While it is easier to use and has been approved by the FDA, it is very expensive, up to $520 per vial and $3,120 per course.

 A course of treatment costs only $700, equivalent to $70/pill.

The emergence of a simple oral drug like molnupiravir would fill all the gaps left by the above treatments. It has proven effective, is easy to deploy on a large scale, and is easy to store and transport around the world because it is a capsule rather than an injection.

In addition, the price of molnupiravir is also much cheaper than remdesivir. A course of treatment costs only 700 USD, equivalent to 70 USD/pill.

Of course, that's still a hefty price tag for many patients. But governments have been quick to approach Merck to order molnupiravir for their own populations. The US has committed to buying 1.7 million courses of molnupiravir for $1.2 billion.

In Asia, Thailand is also negotiating with Merck to purchase 200,000 molnupiravir tablets in its first order, while Japan, South Korea, Taiwan, Malaysia and the Philippines have revealed their plans to buy the drug.

Finally, it must be said that between preventing and fighting Covid-19, prevention is still better than cure, because it is a cheaper and more effective measure . Compared to Covid-19 vaccine doses that cost less than 10 USD, a treatment course with molnupiravir costs up to 700 USD, which is 70 times more.

Therefore, vaccination is still the most important goal at the present time. In addition, we still have to strictly implement other Covid-19 prevention measures such as 5K, keeping distance, wearing masks and washing hands regularly. In addition to treatment drugs, the pillars of previous pandemic response should still be maintained in a consistent and consistent manner.