In dialogue with Clarion, Esteban Domingo explained what the process of lethal mutagenesis and the possible risks of applying it to humans.
While in Argentina and Spain “the million infected covid” is a sinister milestone to which we are approaching, we are about to exceed or have just done, from Madrid, the Spanish virologist Esteban Domingo proposes tame the coronavirus giving him his own medicine.
Viruses continually mutate and use mutations to adapt, to continue multiplying, to pass from one person to another, to survive. If one ‘mutagenizes’ it, that is, one does mutate to lethality, it becomes harmless, “he tells Clarion the virologist from the Madrid Center for Molecular Biology Severo Ochoa.
“This concept of making the virus deteriorate due to an excess of mutations that is achieved by introducing substances into its genetic material is the basis of lethal mutagenesis”, defines it Domingo, who has spent more than four decades studying the behavior of viruses and that year was appointed member of the National Academy of Sciences of the United States, remarkable institution that Abraham Lincoln founded in the middle of the XIX century.
-Why would accelerating the mutations of the coronavirus make it harmless?
-Because those mutations necessary for the adaptation of the virus have a limit and the limit is a certain value above which there are too many mutations and, instead of adapting to the virus, they poison it to the point where it can no longer multiply.
-How is that achieved?
-Adding substances that are put into the genetic material of the virus and make it mutate more than normal. These substances are called “mutagenic” agents and they are what generate the mutations. They are substances that look like “nucleotides” that normally must be put into the genetic material of the virus to perpetuate it. That is, they are similar but they are not identical and then it turns out that they cause more “errors” in the multiplication of the virus. So more mutations are produced and those mutations are errors in the genetic material. There comes a point where these errors are excessive for the virus to continue to function.
-Because it is what happens with all living beings. We all have a very controlled rate of mutation in our cells, but if for some reason that gets out of control, everything starts to deteriorate.
-This mutation is achieved in a laboratory or can it be applied to an infected person?
-In both situations. It was first done in the lab to see if this really worked. There are many studies on this in various viruses. Then there are the experiments that have been done with animals or laboratory plants. And of course, with substances that have passed all the appropriate or necessary toxicity tests for human use, they can be done in people. People know little that there are already two substances that are used for human use, which are called favipiravir and rivadivine, that at least in part its activity is due to lethal mutagenesis. One of these substances, favipiravir, was used for the Ebola virus and is intended to be used in India for Covid-19.
-Could the course of a treatment of this type anticipate the vaccine, taking into account that it also involves introducing a substance into the human body?
-It is an excellent question and very difficult to answer. Right now it is very difficult to predict whether an effective vaccine or effective treatment will arrive sooner. There is a tremendous race, there are many vaccines that are being developed in parallel. At the same time there are numerous studies with antiviral agents, lethal mutagenesis and other types of substances. After many decades in which a vaccine was sought for AIDS, the disease due to the human immunodeficiency virus that was a tremendous pandemic at the end of the last century and even in this century, everyone thought that there could be a vaccine. It does not exist to this day. There are several trials done but there is no effective vaccine against AIDS. In contrast, retroviral treatments have been so effective that they are turning AIDS, which was a deadly disease three decades ago, into a chronic disease. I can tell you the same about hepatitis C. Another example is the flu, but in reverse. For the flu we have a reasonably effective vaccine that needs to be updated. There are also retroviral agents but, without a doubt, the population’s preference is the vaccine.
-Does accelerating the mutation of the coronavirus have contraindications?
-From the point of view of the danger that, due to the mutations, the virus mutates to be worse, that is, that we are creating, due to the mutations, a very virulent virus, the probability is extraordinarily small. The fact that a worse virus is created during a lethal mutagenesis procedure has never been described in any laboratory experiment. There is another aspect, not so clear: those agents that cause mutations in viruses, could they not also cause mutations in people? That is, could the person receiving the treatment have mutations in their own cells as a side effect? And the answer is: the substances that are being approved for use as antiviral agents by lethal mutagenesis have been selected because they are not precisely capable of mutating the cells of organisms that carry the virus. That is, they have been selected because they manage to mutate the virus but not the cells. That said, there is no antiviral treatment that is completely free of side effects. But there is no reason to believe that the antiviral strategy by lethal mutagenesis will have adverse effects beyond what is usual in medical practice.
-Here, in Spain, between the first wave of the pandemic and the current one, in this second wave the virus appears to be less lethal and infects younger people. Could the cause be a mutation of the virus?