Some scientists have expressed concern that an anti-viral COVID-19 drug being rolled out across the United States could help fuel the emergence of dangerous new variants.
The anti-viral pill molnupiravir, developed by Merck and Ridgeback Biotherapeutics, was authorized for emergency use by the Food and Drug Administration (FDA) in the United States on December 23, 2021, after an advisory panel narrowly endorsed the drug Was.
The pill is designed to treat adults with mild to moderate COVID-19 symptoms who are at high risk of severe illness.
Molnupiravir is available by prescription only and should be started as soon as possible after a COVID-19 diagnosis and within five days of symptom onset. The FDA was clear in announcing the authorization that the use of the drug would be limited to people at high risk for whom alternative treatments are not “accessible or medically appropriate.” It should not be used for more than five consecutive days.
Initially hailed as a potential game-changer because it can be taken at home, the drug has been shown to reduce the risk of hospitalization and death from COVID-19 by up to 30 percent in these patients – Originally claimed to have less efficacy than Merck.
With downregulated efficacy data, some concerns have been raised about the drug’s safety and that it could possibly alter human genes. While the risk to adults is low, according to data from animal studies, the FDA has not authorized the drug for individuals under 18 or pregnant.
In addition, some experts have raised concerns about the possibility that the use of the drug could lead to the emergence of new COVID-19 variants, such as Delta or Omicron, which are highly transmissible and/or You can avoid the protection offered by vaccines. ,
Molnupiravir works by interfering with the replication of the SARS‑CoV‑2 virus – which causes COVID-19, once it enters the body’s cells. It does this by introducing errors into the genetic code of the virus. Introducing enough errors eventually stops the virus from replicating and the patient can clear the pathogen from their body.
But some scientists caution that during this process of mutation, there is the possibility that new forms may emerge under certain circumstances—though other experts have underestimated such fears.
“I am very concerned about the potential consequences now that mollupiravir has been approved,” said Michael Lin, associate professor of neurobiology and bioengineering at Stanford University. newsweek, “It will only be a matter of time, perhaps a very short time, before a lucky set of mutations occurs to create a variant that is more transmissible or immunogenic.”
“Mutations are those that naturally make the types of anxiety that are more infectious or immunosuppressive, like Delta or Omicron,” he said. “The drug simply speeds up that natural process. The hope is that in enough days all the viral copies will have so many mutations that no copy can act.”
But Lin said he is concerned that in the real world, there is the possibility that a mutated virus could pass from person to person taking mollupiravir, citing the drug’s relatively modest efficacy.
“For cases that get worse so that people have to go to the hospital, this drug only prevents this from happening 30 percent of the time. That means 70 percent of the time the virus isn’t being eradicated quickly enough to make a difference.” And we know that COVID patients going to hospitals are highly contagious.”
Lin said the risk may increase when a patient does not properly follow the drug’s dosing schedule.
“This treatment is an oral one, so it’s going to rely on patients taking their pills. Patients are notoriously poor at completing a course of pills correctly. They’ll forget, or they’ll feel side effects.” And stop, or they’ll feel better and think they don’t need to run out of pills.”
“In any of those conditions the virus would have carried some mutations, but not enough to kill all virus copies,” he said. “The survivors have now mutated, may have acquired immunodeficiency, and may infect others.”
Merck has not supplied data showing that the drug eliminates the virus in patients who are less likely to eliminate the virus and most likely to go to hospital—that is, those who are immunocompromised. In its emergency authorization letter, the FDA requested that the company provide this data by April of this year.
According to Lin, the “very low efficacy alone” should have disqualified the drug from approval because it was simply an inferior alternative to other therapeutics such as fluoxetine, a monoclonal antibody, or Pfizer’s own oral COVID-19 anti-viral pill Paxlovid. will work as Trials that have shown it to be 89 percent effective in preventing hospitalization and death in high-risk patients.
“Even if the drug was great we wouldn’t take such a risk, but this drug is worse than any other drug that has been asked for approval for COVID19. It’s totally not worth it.”
Dr. William Haseltine, an expert on the COVID-19 epidemiology and former Harvard Medical School professor known for his groundbreaking work on HIV/AIDS and cancer, is among other scientists who have researched mollupiravir and its potential to fuel I have expressed concern. The emergence of new variants.
Haseltine, the founder of several biotechnology companies who spent much of his early career working on HIV antivirals, said newsweek: “I am very concerned. And my concern is shared by many other scientists.”
According to Haseltine, even under ideal conditions, patients treated with mollupiravir release viable live virus for two or three days during their treatment.
“Unfortunately, those virus scenes have not been made public,” he said. “But despite this, it is a drug that can seriously aggravate an already bad condition.”
As the drug is dispensed to millions of people across the country — the US pre-ordered 3.1 million courses, though supplies are currently tight and there is limited access — the risks rise, he said.
“Of all the antiviral drugs I’ve ever seen, this is by far the most potentially dangerous. The more people who take it, the more dangerous it is,” Hasseltine said.
There is some evidence from pre-pandemic experiments that other coronaviruses—the family to which SARS-CoV-2 belongs—may become resistant to mollupiravir. Development of the drug, which was initially designed to treat influenza, began in mid-2010.
When the anti-viral was tested against two other coronaviruses—MERS-CoV and mouse hepatitis virus (MHV), the researchers observed an increase in mutations, including the key spike protein, which allows pathogens to attach to and attach to living cells. Enables access.
In fact, for MERS, which is closely related to SARS-CoV-2, the researchers found more than 100 mutations on the virus’s genome. It has more mutations than the highly mutated Omicron COVID-19 variant.
While these experiments demonstrated replication loss, MERS and MHV viruses can still survive and replicate.
“While it is possible that at the optimum concentration, the drug could cause enough mutations to prevent replication and onward transmission. [SARS-CoV-2,] The effect of the sub-optimal dosage is still largely unknown,” Hasseltine wrote in an article. Forbes,
In an FDA analysis of the results of Merck’s mollupiravir clinical trial for the treatment of SARS-CoV-2, officials found that virus mutations were more prevalent in people who were given the drug than those who received a placebo.
FDA researchers told the advisory panel – which voted 13 to 10 in favor of the emergency authorization recommendation – that some of these structural changes were similar to those seen in major COVID-19 variants such as Delta. But FDA researchers said the risk of new forms emerging in individual patients was low.
One of the panel members who voted no, James Hildreth, president of Meharry Medical College in Tennessee, said Merck should do more to measure the risk of such an event.
“Even if the probability is very small, one in 10,000 or 100,000, that this drug will induce an escape mutant, which we haven’t covered, that would be catastrophic for the whole world,” he told the panel.
in a statement made to newsweek, a Merck spokesman said: “There is no evidence that any antiviral agent contributed to the emergence of circulating variants. During pandemics, uncontrolled viral replication and the widespread absence of variants due to continued transmission have emerged. Available treatment options and low levels of vaccination. Antivirals such as molnupiravir, as they help address these issues, may become an important part of the solution.”
many other scientists who newsweek People contacted for this article said they were not overly concerned about the potential for mollupiravir to generate new and potentially dangerous forms.
Dr. Douglas Richman, Professor of Pathology and Medicine at the University of California San Diego newsweek: “I am personally not concerned that molanupiravir presents a risk of emerging virus resistant to concern.”
The theoretical risk of the drug potentially being capable of damaging human genes and its “less than optimal efficacy” are “real concerns,” the researcher said.
Dr. John Williams, Professor of Pediatrics at the University of Pittsburgh School of Medicine newsweek The risk of drug-resistant viral mutations is “low”.
“I and the scientists I’ve been in contact with are not particularly concerned that this drug will lead to the emergence of a new type of anxiety. The drug’s trials against SARS-CoV-2 in cells and animals, as well as other Even against RNA viruses, the drug causes lethal mutations in the virus and had a high barrier to developing resistance.”
Even if drug-resistant mutants were generated, Williams said, there’s no reason to think they would behave any differently to the variants already running.
“In fact, drug-resistant viruses are often ‘weaker’ than ‘wild-type’ viruses,” he said.
Shankar Swaminathan, an infectious disease specialist at the University of Utah School of Medicine, said the emergence of new forms in patients taking molanupiravir “is unlikely,” at least on a large scale, for a number of reasons.
“The high rate at which mutations are induced in the viral genome can lead to so-called destructive mutations, which render the virus unable to replicate. Therefore the need to generate viable viruses capable of surviving and circulating at high levels generally Not likely. Rates are higher than normal during normal untreated infections.”
“We have no evidence that such [new variants] Survival treatment in normal individuals in the study. But the frequency at which these may exist is not known for certain.”
Still, Swaminathan said the risk of generating the new variant may be higher in immunocompromised patients who are taking the pill, even though the risk is still low.
“In situations where viral elimination is impaired, as we have seen in patients with compromised immune systems, viruses persist and come through each round of antiviral therapy or antibody treatment, escape eradication, and mutate. with those who have been chosen to be resistant,” he said. “We just don’t know whether this is likely or how often it can happen in an immunocompromised patient.”