A Possible Side Effect of Merck's Oral COVID-19 Drug should alarm the Public

A rush for molnupiravir's approval could lead to disaster.

For anyone who has been keeping track of the narrative around COVID-19 therapeutics you will know that this arena has been filled with inconsistencies. Hydroxychloroquine, which gained EUA usage in 2020 had its EUA rescinded and was demonized over a later discredited study published in the Lancet. Ivermectin, which has been used for decades and showed some possible efficacy against SARS-COV2 infection was castigated, and has recently been labeled as a “horse-dewormer” by the mainstream press to delegitimize the drug. It’s hard to look at the castigation of these decades old drugs that have been administered to millions of people and available over the counter worldwide as anything else than a form of institutional capture.

Now Merck, the pharmaceutical company who held the original patent for Ivermectin, is coming out with a new therapeutic for SARS-COV2 called molnupiravir (I pronounce it as mal-new-pier-ra-vir).

In a press release on June 9th the Biden administration announced that it will spend over $1.2 billion to procure around 1.7 million courses of the drug. Following these numbers this would indicate that a course of molnupiravir could cost around $700, far more than what hydroxychloroquine and Ivermectin would cost (note though, this is not an argument in favor of HCQ or Ivermectin, but bringing awareness to the high cost of this therapeutic). Remember that initial reports of remdesivir indicated a 5 day course of the drug would cost around $3,000 dollars.

Unlike remdesivir, molnupiravir can be administered orally, meaning that it can be used for outpatient treatment as well as a prophylaxis (there does seem to be an orally bioavailable form of remdesivir being developed).

So here we have a large effort to push for an expensive, outpatient therapeutic that can also be used as a prophylaxis. What could go wrong?

Let’s look at how molnupiravir works. To start off, note that molnupiravir IS NOT similar in structure to Ivermectin as many people have claimed. Molnupiravir is a nucleoside analogue, the same class of drugs that remdesivir is in, meaning that it is a modified version of the nucleosides utilized in our bodies.

Here are the structures below. Note that molnupiravir is an N-4-hydroxycitidine meaning that there is an -OH group added to the cytosine base.

Molnupiravir (shortened to NHC) acts as a mutagen, meaning that it alters (mutates) the genome of SARS-COV 2. Its mechanism of action first requires it to be inserted into a viral genome during the replication process. Because it looks similar to Cytidine (C) NHC competes with C for insertion into the genome. After being inserted, a second virus cycle must occur. During the next replication cycle a Guanosine (G) could be inserted to base pair with NHC. However, the RNA dependent RNA polymerase (RdRp) may mistake the NHC as a Uracil (U) and add in an Adenosine (A) instead of the correct G. This selective mutation will lead to the downstream production of the wrong proteins. Therefore, unlike other nucleoside analogues that operate to directly stop viral replication, molnupiravir works over several viral replication cycles.

The theory at work here is that continuous incorporation of the wrong base will lead to the accumulation of viral mutations, causing the virus to kill itself off due to the excessive number of accumulated errors, a scenario labeled as a “viral error catastrophe”.

Here is a schematic taken from Gordon et al. 2021 highlighting this scenario. Note the base change in C between 3 and 3’.

Taken from Gordon et. al. 2021. C indicates the incorporation of NHC (M) into the genome, leading to the wrong insertion of (A) in a second replication cycle. As indicated in (B), NHC may be recognized as a C and hydrogen bond with G or it may be recognized as a U and hydrogen bond to A.

Phase 1 and 2 trials of NHC in mice and ferret models infected with SARS-COV2 showed large improvements, and in human trials there was evidence of no viral load by day 5 of the trial. There were even very few acute toxicities listed.

Although this seems like it could be a wonder drug for SARS-COV2, NHC’s therapeutic capabilities could lead to catastrophic consequences down the road.

Remember that NHC acts as a mutagen and can alter the viral genome. Many nucleoside analogues are broad spectrum therapeutics, meaning that they can affect many cells in your body since our cells are not able to differentiate between the drug and the proper nucleosides.

This side effect is prominent in many cancer patients receiving chemotherapeutics. Many chemotherapeutics are nucleoside analogues, and are administered in an attempt to utilize the rapidly dividing nature of cancer cells, but this also means that many of our rapidly dividing cells can become targets as well. That’s why many of the side effects of chemotherapies include hair loss, dry skin and brittle nails, dry eyes, and GI issues.

In the case of NHC, NHC may be inserted into the genome of noninfected cells, leading to the accumulation of mutations and possibly to the development of cancer.

There is some evidence to suggest this may occur with NHC as indicated by a study by Zhou et. al. 2021 In The Journal of Infectious Disease. In this study the researchers found that exposure to NHC caused a mammalian cell line to mutate and resist cell death when exposed to a toxin, which indicated a gene mutation occurred.

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The authors noted:

SARS-CoV2 infection results in an age-related acute respiratory disease spectrum that can be life-threatening, especially in the elderly and individuals with select underlying comorbidies [14]. rNHC has the potential to have therapeutic benefit in this setting. However, there are risks for the host in that the same mutagenic activity that impacts viral replication has the potential for incorporation and mutagenesis of host DNA. This risk can be inferred based on the common intermediate of the ribonucleoside diphosphate shared in the synthesis of both ribonucleoside triphosphates and 2′-deoxyribonucleoside triphosphates. The concern would be that mutations in host DNA could contribute to the development of cancer, or cause birth defects either in a developing fetus or through incorporation into sperm precursor cells…

We take this as evidence that in exposing the viral population to mutagenesis in its RNA form, the host is likely to be exposed in its DNA form. It seems unlikely that a short course of therapy would spare the host from this exposure because both RNA precursors that affect the virus and DNA precursors that would affect the host pass through the common ribonucleoside diphosphate intermediate.

Although NHC is administered as a ribonucleoside, it can be transformed into the deoxynucleoside form and utilized by our own cells, indicated by the mammalian cell culture results, and can lead to mutations and possibly cancer.

This finding should alarm people; here we see the push for a therapeutic where only acute toxicity has been measured with no measurement of long term side effects, that is expected to be dished out to the public in the millions.

Remember that the demonization of HCQ was based on possible cardiac arrhythmias, and in the case of Ivermectin its “lack” of effectiveness, both of which are still up for debate (I will cover the controversy around HCQ in a later article). What seems like very loose standards to target previous drugs that have had a long history of usage is now being ignored when it comes to a brand new drug with very few clinical studies. Again, this isn’t an argument in favor of HCQ or Ivermectin, but points to the hypocrisy of how these drugs are being presented. When some drugs must meet the golden standard of rigorous testing and others can pass by with the bare minimum one has to question what is going on in order to disregard such blatant hypocrisy.

Unfortunately, this has happened previously in regards to remdesivir. When remdesivir was first touted out it was considered a miracle therapeutic in the fight against SARS-COV2, with Dr. Fauci stating that it would be immoral to not provide the drug based on the initial clinical results. Note that in most clinical trials a therapeutic must meet the gold standard of reducing mortality. In the case of remdesivir, the initial clinical trials boasted a reduction of hospital stay from 15 days to 12 days as significant, leading to its widespread adoption. However, it’s now clear that remdesivir is not as effective in treating SARS-COV2 as once claimed. Whether this is due to the timing of remdesivir’s administration or possible adverse reactions, the notion that a $3,000 course of a therapeutic was pushed for while no outpatient therapeutics were available, or demonized, is concerning.

Looking up molnupiravir in the mainstream press you’ll notice that none of them refer to this drug as a “mutagen”, but instead as an RNA polymerase target. This may seem like a game of semantics, but the notion that a drug can act as a possible mutagen, and therefore a carcinogen, and is not being discussed in the mainstream means that millions of Americans may be left uninformed about these possible side effects, and may possibly put themselves at harms risk if they are prescribed this drug.

It is even more concern when we look at the lawsuit against Johnson & Johnson. Johnson & Johnson was recently sued due to the alleged link between their talcum powder and ovarian cancer, a product that has been in mainstream use for decades and is now only just receiving attention about this possible cancer link.

Imagine a drug, dispensed in the millions, to uninformed consumers who may develop cancer years into the future, and the ramifications will be disastrous. With the questionable status of the FDA, and even more widespread skepticism when it comes to previous FDA approved drugs, it is more apparent now than ever of the institutional capture that is at play here.

Of all the drugs that should undergo rigorous testing procedures this should be at the top. Whether or not this occurs is left to be seen, but following with what we’ve seen so far I’ll remain skeptical.

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