How powerful is the COVID-19 drug Molnupiravir named after Thor’s hammer Mjölnir?

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

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

“We predicted that from laboratory studies, and now, the results [trong thử nghiệm lâm sàng giai đoạn III] This is confirmed. You know, this drug is named after Thor’s hammer, and it will be a hammer against SARS-CoV-2 no matter how they mutate.“, said Dean Li, Merck’s head of R&D.

Based on very positive Phase III clinical trial results, Merck and molnupiravir manufacturer Ridgeback Biotherapeutics are applying for an emergency use authorization with the U.S. Food and Drug Administration (FDA) ), with the desire to bring 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 has the ability to target an important enzyme of the SARS-CoV-2 virus called RNA-dependent RNA polymerase (RdRp). This long name can be called a transcription enzyme for short, as it catalyzes the RNA replication of SARS-CoV-2, which gives the virus the ability to multiply and multiply rapidly once enter the patient’s lungs.

Once introduced into the body, the molnupiravir molecule will find the virus and deal a fatal blow to its RNA polymerase. This thunderbolt stems from the fact that molnupiravir can forge a base nucleotide called cytidine (C).

Once attached to the virus’s RdRp enzyme, molnupiravir halts its reproductive cycle, creating genetic mutations that kill or inactivate the SARS-CoV-2 virus. The researchers call this a “disaster for the virus”, because once the rate of genetic mutations exceeds a certain number of replication errors, the virus will not be able to survive and cause disease.

The mechanism of action of molnupiravir is therefore stronger than that of the currently used drug remdesiver. While remdesiver uses a similar mechanism by replacing the nucleotide Adenosine (A) in the virus’s replication machinery, it is only able to prevent the virus from replicating without causing mutations to kill them like what the drug does. molnupiravir can do it

Before the COVID-19 pandemic, Merck was working on molnuporavir as a drug to fight the flu virus. However, in March 2020, when COVID-19 peaked and became a global pandemic, they found themselves needing to change direction to create an anti-SARS-CoV-2 drug based on the principle of enzyme attack. copy that.

Theoretically, these nucleoside decoys have raised concerns that they also cause problems with the replication enzymes of human cells. For this reason, the drug has not yet been tested and indicated for pregnant women.

However, to date, all animal and clinical trials have shown molnuporavir to be highly safe. The Merck scientists found that the rates of side effects in the drug and placebo groups were similar, at 11 percent and 12 percent, respectively.

The results of the Phase III clinical trial are extremely promising

Before being used for SARS-CoV-2, Merck said it had tested the drug molnuporavir on other coronavirus strains, namely SARS-CoV and MERS-CoV. It was shown 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 cells infecting SARS-CoV-2 from the human respiratory tract.

In the latest phase III clinical trial that involved 775 COVID-19 patients, Merck selected adults susceptible to severe illness and death to receive the drug molnupiravir. They must be people with at least one risk factor for poor treatment outcomes, such as obesity, diabetes, heart disease, or age 60 or older.

Half of the volunteers will be given two molnupiravir tablets a day, 12 hours apart, for 5 days. The other half of the volunteers received only a placebo and the same standard of care as other normal COVID-19 patients.

After 29 days of follow-up, 53 of the 377 participants who received placebo were hospitalized with severe progression of COVID-19, and eight of these individuals died. In contrast, in the group of 385 people who received real molnupiravir, only 28 people were hospitalized and no patients died.

In other words, only 7.3% of patients on molnupiravir were hospitalized or died, compared with 14.1% in the placebo group. This is the basis for Merck’s claim that its COVID-19 drug is more than 50% effective.

The manufacturer notes that they have also taken samples of patients participating in the trial for gene sequencing, thereby identifying up to 40% of patients infected with the variant. This means that the drug molnupiravir has the ability to work against different strains of COVID-19, including Delta, Gamma and even Mu.

“Bring Me COVID”

While there are several treatments for COVID-19 available, the downside of all of these methods is that they are difficult to use, expensive, and not very effective.

The first drugs used during the pandemic, ivermectin and hydroxychloroquine, were once considered hopeful but ultimately failed to prove effective. Next, the method of transferring serum from recovered people or monoclonal antibodies is more effective, but it is 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, preserving and transferring to new patients.

The most common treatment for COVID-19 now is using remdesivir, a drug injected into a vein. Although it is easier to use and has been approved by the FDA, it is very expensive, up to 520 USD / vial and 3,120 USD / course.

The arrival of a simple oral drug like molnupiravir will fill in all the gaps that these treatments are telling. It has proven to be effective, easy to deploy on a large scale, and easy to store and ship around the world because it is a capsule, not an injection.

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

Of course, that’s still a pretty hefty price to pay for many patients. But governments quickly approached Merck to order the drug molnupiravir for their own use. The US has committed to buy 1.7 million courses of molnupiravir for $1.2 billion.

In Asian countries, Thailand is also negotiating with Merck to buy 200,000 molnupiravir tablets in the first order. Along with that, Japan, Korea, Taiwan, Malaysia and the Philippines have revealed their drug purchase plans.

Finally, it should be said that between the prevention and combat of COVID-19, prevention is better than cure, as it is a cheaper and more effective measure. Compared to doses of the COVID-19 vaccine that cost less than $10, a course of treatment with molnupiravir costs up to $700, which is up to 70 times more.

Therefore, vaccination is still the most necessary goal at the present time. In addition, we still have to strictly follow other COVID-19 prevention measures such as 5K, keeping distance, wearing masks and washing hands often. In addition to medication, the pillars of the previous pandemic response should remain consistent and consistent.

Refer to Vox, Arstechnica, Science