Merck’s newly announced pill to treat Coronavirus Disease 2019 (COVID-19) based on the molnupiravir compound has the downside of serious mutagenic risks in mammalian cells, according to researchers. In response, the pharmaceutical giant has disputed the study and its methodology, resulting in an unclear situation for consumers.
Molnupiravir had demonstrated a 50 percent success rate in preventing hospitalization and death over the placebo group in a clinical trial, said an announcement from the company on Oct. 1, causing shockwaves in the price of various pharmaceutical stocks.
The press release stated the trial was truncated halfway through at the advice of the Food and Drug Administration and that Merck would seek Emergency Use Authorization as soon as possible.
The celebration has not been without its controversy. Only a few days later, news that the now-resigned Francis Collin’s NIH and Anthony Fauci’s NIAID had funded development of the compound at Emory University to the tune of $35 million since 2013 emerged in conjunction with analysis from a Harvard researcher that Merck had resold the product to taxpayers for $1.19 billion USD at a 3,500 percent markup over production costs.
At the same time, Barron’s reported on Oct. 5, updating the article on Oct. 8, that molnupiravir’s efficacy was not all roses, as it had shown to be mutagenic in mammalian cells, “Molnupiravir works by incorporating itself into the genetic material of the virus, and then causing a huge number of mutations as the virus replicates, effectively killing it,” reads the article.
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“In some lab tests, the drug has also shown the ability to integrate into the genetic material of mammalian cells, causing mutations as those cells replicate.”
Raymond Schinazi, a professor at the same Emory University where molnupiravir was developed, told the outlet, “Proceed with caution and at your own peril.”
According to Barron’s, Schinazi, who was not involved in the development of molnupiravir, has studied NHC, the active compound that the Merck pill synthesizes in the body to produce its antiviral effect, for decades.
Schinazi was further paraphrased as stating that “he did not believe that molnupiravir should be given to pregnant women, or to young people of reproductive age, until more data is available.”
However, this is where the waters become muddy. Schinazi, the article notes, nonetheless has something of a conflict of interest, “He was a founder of the biotech Pharmasset, which he says considered developing NHC as a treatment for hepatitis C in 2003, but chose not to because of the risk that it could cause mutations.”
Barron’s continues, “Pharmasset created the hepatitis C drug Sovaldi, and Gilead Sciences (GILD) eventually bought the company for $11 billion.”
Gilead Sciences is the company that controls the first FDA-approved treatment for COVID-19, remdesivir.
In an October of 2020 article published in Science critical of remdesivir’s approval, the author states that the “FDA never consulted a group of outside experts that it has at the ready to weigh in on complicated antiviral drug issues.”
“The European Union, meanwhile, decided to settle on the remdesivir pricing exactly 1 week before the disappointing Solidarity trial results came out. It was unaware of those results, although Gilead, having donated remdesivir to the trial, was informed of the data on 23 September and knew the trial was a bust.”
The Solidarity trial the outlet refers to was conducted by the World Health Organization and “showed that remdesivir does not reduce mortality or the time COVID-19 patients take to recover,” according to the report.
Schinazi’s opinion was backed up by research he conducted with Ralph Baric and his team at the University of North Carolina Chapel Hill, a researcher and an organization that has ties to the Wuhan Institute of Virology’s gain-of-function on bat coronaviruses research.
In a May 7 study, Baric’s UNC team notes in the Abstract, “Besides remdesivir, which blocks the replication of several coronaviruses, limited therapeutic options are available for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.”
The experiment found that NHC was highly effective at introducing lethal mutagenesis into SARS-CoV-2, but that “NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.”
An April of 2020 study by a similarly constructed Ralph Baric/UNC team found molnupiravir was very effective against the original and much more deadly SARS coronavirus and Middle East Respiratory Syndrome (MERS), another highly infectious and fatal coronavirus.
UNC researcher Zhou Shuntai was rather direct in statements he made to Barron’s for their article, “There is a concern that this will cause long-term mutation effects, even cancer.”
“Biochemistry won’t lie. This drug will be incorporated in the DNA,” said Zhou.
In a July 12 Letter to the Editor published in the Oxford Journal of Infectious Diseases, Merck scientists took issue with the UNC study’s findings and methodology, “In contrast, we have conducted a more comprehensive series of in vitro and in vivo genotoxicity studies, which, based on the totality of the data, demonstrate a low risk for genotoxicity…in clinical use.”
“It is important to note that the assay conditions used by Zhou et al for their in vitro HPRT assay differed significantly from standard protocols conducted under regulatory test guidelines,” continued the criticism.
“The mutation results provided by Zhou et al were reported as total mutant colonies rather than mutant frequency, which does not allow for comparison of negative and positive control data to publicly available literature.”
The Letter continues, “The rationale for the NHC concentrations used in the assay (or concurrent control compounds) was not provided. To avoid potential false-positive results, the highest concentration tested should avoid producing precipitation in the culture media, marked changes in pH or osmolality, or excessive cytotoxicity.”
“Finally, information regarding the origin and purity of the NHC material used was not provided, and it is uncertain whether the stability or impurity of the material was characterized.”
A third party opinion was provided by Barron’s from NYU Grossman School of Medicine professor in the department of microbiology, Nathaniel Landau, who said, “Given the possibility that the drug could be incorporated into cellular DNA, it will be very important to demonstrate a lack of cancer in animal models and in humans.”
“Even though it looks good in preliminary animal models, it will be important not to rush this into clinical use before being very confident that it does not cause cancer even at very low frequencies.”