First COVID-19 drug may induce mutations and produce more deadly mutants

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Virologists warn: the first oral COVID-19 drug may induce virus mutations and produce more deadly mutants, even cause cancer!

A study published in “Science” on November 7 shows that the oral anti-coronavirus drug Molnupiravir approved on Thursday that can reduce the risk of hospitalization or death by about 50% may not be an anti-coronavirus “panacea”.

William Haseltine, a famous virologist who worked on HIV and the Human Genome Project at Harvard University, pointed out that by inducing virus mutations, the pill may stimulate the emergence of new virus variants that are more dangerous than today.

It can cause mutations in the patient’s DNA, which may lead to cancer or birth defects. However, some people also said that when SARS-CoV-2 replicates in infected people, it is very good at making mutations naturally. The mutations may be generated from here, so there is no need to panic too much.

Break “is an infectious disease vaccine Terminator” cognitive Thursday, the first COVID-19 for the treatment of oral antiviral drugs – Merck ( Merck ) of Molnupiravir been approved by the UK’s Medicines and Healthcare Products Agency .

However, this approval for high-risk groups was carried out when a well-known virologist suggested that the use of Molnupiravir may cause more harm than good , and it may release a new and more deadly variant of SARS-CoV-2 .

Other virologists say this concern is worth tracking, but it is mostly hypothetical at the moment. Aris Katzourakis , a virus evolution expert at the University of Oxford, said: ” I don’t think we will stop using life-saving drugs because of possible or impossible risks .”

On November 7 , the researchers published an article titled ” A prominent virologist warns COVID-19 pill could unleash dangerous mutants. Others see little cause for alarm ” in ” Science ” .

First COVID-19 drug may induce mutations and produce more deadly mutants

Molnupiravir is an experimental antiviral drug developed by Merck and Ridgeback Biotherapy , named EIDD-2801 , which is comparable to the new drug Remdesivir . Its role is to interfere with virus replication .

EIDD-2801 is similar to Remdesivir, both of which work by mimicking ribonucleotides (the main component of RNA molecules).

In the process of virus replication, the molecules of these drugs can be incorporated into the viral RNA chain to replace the nucleic acid base sequence produced by some viruses during normal replication, causing errors in the nucleic acid sequence of virus replication, and these fatal nucleic acid alignment errors continue to occur.

Accumulation, that is, error mutation, can ultimately prevent the virus from replicating, expanding, and spreading .

Last month, officials from Merck and Ridgeback announced the results of a clinical trial that found that giving COVID-19 patients early in the disease can reduce their risk of hospitalization and death by 50% .

However, the drug’s ability to mutate RNA has raised ongoing concerns that it will cause mutations in the patient’s own genetic material, possibly leading to cancer or birth defects; studies to date have not confirmed these concerns .

First COVID-19 drug may induce mutations and produce more deadly mutants

Now, William Haseltine , a virologist who has been engaged in research on HIV and the Human Genome Project at Harvard University, as the chairman and president of ACCES Health International, and an internationally recognized COVID-19 pandemic expert , has proposed that by inducing viral mutations, Molnupiravir may stimulate more than it is today.

The emergence of more dangerous new virus variants . Haseltine outlined his concerns in a blog post on Forbes on Monday. He said: ” While we are deeply concerned about the new variant, you are putting a drug with a powerful mutagen into circulation . I can’t think of anything more dangerous than this.”

First COVID-19 drug may induce mutations and produce more deadly mutants

He pointed out that patients receiving antibiotics and other drugs usually do not complete the prescribed course of treatment, which can allow drug-resistant bacteria to survive and spread.

If a COVID-19 patient feels better after a few days and stops taking Molnupiravir, Haseltine is worried that the mutant strain of the virus will survive and may spread to other people .

Haseltine said: “If I try to create a new and more dangerous virus in humans, I will give the infected person a subclinical dose of Molnupiravir.”

Raymond Schinazi , an infectious disease expert at Emory University , said: “ The possibility (of mutation) exists .” But no one he contacts with scientific insiders is as worried as Haseltine. Katzourakis said: “I disagree with this. If you force an organism to mutate more, it is more likely to be harmful to the virus.”

The basis for Haseltine’s concerns is that studies have shown that coronaviruses can survive the mutations induced by Molnupiravir . For example, two years ago, Vanderbilt University virologist Mark Denison and his colleagues repeatedly exposed the coronavirus to a sublethal dose of a drug called EIDD-1931 to test whether drug-resistant viruses would emerge .

They report that in a population of two coronaviruses, the mouse hepatitis virus and the virus that causes Middle East respiratory syndrome-30 rounds of such drug treatments resulted in as many as 162 different mutations, and these mutations did not kill them. Virus . But Denison pointed out that his research did not classify mutations in individual viruses; instead, there were as many as 162 mutations in cell populations infected with one of the two coronaviruses.

Most mutations are harmful to the virus and slow down growth. Denison said: ” If I draw any conclusion from our research, it is that if the virus tries to adapt, for example, through resistance to Molnupiravir, it will continue to develop harmful mutations .”

However, Cambridge University’s Microbiologist Ravindra Gupta warned that the mutated virus is more likely to spread in patients who have compromised immune systems and are most likely to take Molnupiravir. He said that because the vaccine is less effective in protecting these patients, “These people are precisely the people most likely to receive [Molnupiravir].”

Daria Hazuda , Merck’s head of infectious disease research , pointed out that the company has not found any evidence that people taking Molnupiravir are producing viruses with new dangerous mutations .

Among the patients who completed the 5-day course of treatment, Hazuda said, ” We did not see any infectious virus”, let alone mutated virus .

The mutations that occur in this process are random and do not focus on a specific gene that makes the virus more likely to survive. There is no evidence of any selection bias .

In addition, Hazuda and others pointed out that SARS-CoV-2 is very good at making mutations naturally when it replicates in infected people .

Katzourakis said: ” There is no lack of virus mutations .” The more important question is whether Molnupiravir provides selective pressure to promote the virus to develop in the direction of transmissibility or toxicity . “I find it hard to imagine,” he said, “but I can’t rule out this possibility .”

Denison and others say that it is more likely that the use of Molnupiravir will result in the emergence of a virus that is no longer lethal or spreadable but is resistant to the drug, which is a common result of anti-infective drugs .

However, news on Friday said that another antiviral drug produced by Pfizer is very effective against SARS-CoV-2, which shows a way to prevent resistance: using two drugs in combination, which is compatible with the treatment of HIV and The multifunctional strategy for other infections is the same .

On November 30, the U.S. Food and Drug Administration Advisory Committee (FDA) will review possible emergency use authorization of Molnupiravir in the United States .

Reference:

https://www.science.org/content/article/prominent-virologist-warns-covid-19-pill-could-unleash-dangerous-mutants-others-see-little-cause-alarm

First COVID-19 drug may induce mutations and produce more deadly mutants

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