The Genetic Code, Remdesivir, and COVID-19: A Pregnancy Perspective

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Now that the COVID-19 pandemic has been going on for some time, in all likelihood you are quite aware that the disease-causing agent, SARS-CoV2, is a virus, even if you are not exactly sure what a virus is. Given the millions of people whom the SARS-CoV2 virus has infected, given ongoing efforts to develop COVID-19 vaccines, and especially, due to encouraging clinical data that were released this past April regarding a drug called remdesivir, semi-celebrity talking heads have been on various news programs trying to explain to viewers —non-scientists and non-physicians—what the virus does and also what the various experimental treatments do. As happens sometimes in science communication, sometimes this leads to misuse of scientific and medical terminology, often by well meaning people who are experts.

Specific to COVID-19, a term that you may be hearing frequently from talking heads explaining the SARS-Cov2 virus and the drug remdesivir is the term “Genetic Code”. I have capitalized the words “Genetic” and “Code”, because “Genetic Code” is “the Genetic Code”. It’s a proper noun, a very specific thing, rather than something that is different in one setting or another. But you wouldn’t know this, given how the term “Genetic Code” is often used. I should actually say abused. What you hear often when experts try to explain genetics to non-biologists is “your genetic code this”, “your genetic code that”, or, much worse, “the genetic code of the virus.” This is very wrong, and actually, when it comes to the SARS-CoV2 viruses (along with most viruses), you should keep the following idea in mind:

The virus does not have a Genetic Code. It needs the Genetic Code of the cells that it infects.

What the SARS-CoV2 virus has is a genome. A genome is a collection of genes. In viruses, a genome can be stored, either in the form of DNA, or RNA. In the case of SARS-CoV2 and all other coronaviruses, RNA is the genetic material, the molecule in which the genome of the virus is encoded. The genome, whether of a virus, a microorganism, a mouse, or a person, is like a group of files of documents on your phone or computer. A genome is content. It is a message. It is a message consisting of genes and each gene in the virus is a recipe for a protein.

In contrast, the Genetic Code is a translation system. It is coding through which genetic messages are translated from the language of DNA and RNA into the language of proteins. It is not the messages themselves, which raises some questions, beginning with: Why do people who are being interviewed as experts use the term “Genetic Code” in the wrong way? Since they tend to be physicians and some are even biologists, it’s extremely unlikely that they don’t know what the Genetic Code is. The term and its meaning is taught first in high school biology, then in college biology, and then over and over again. Rather, it seems that they are misapplying the term, thinking that viewers and listeners in our device-dominated culture cannot relate to anything other than computer talk. In other words, they think that you are stupid in a geeky sort of way.

If you want to go with a computer analogy, then the correct way to think of the Genetic Code is as a computing language, like Java, C++, and Python. This raises another question: What does the SARS-Cov2 virus bring into the cells that it infects? The answer is that the virus introduces its genome into the host cells, which in the case of coronaviruses does not include anything analogous to computer languages. Rather, the coronavirus genome is 100 percent content that will be reproduced in the infected cell using the exact same language, the same Genetic Code, as in other people, and even other species.

In a previous post, we learned that the SARS-CoV2 virus infects human cells by first attaching to a protein called the ACE 2 receptor. Now, the virus consists of a strand of RNA surrounded and protected by a kind of shell that consists of proteins and a fatty membrane that is just like the membrane that surrounds cells. As you may know from doing your laundry, and hopefully from washing your hands, fatty substances tend to dissolve when inundated with detergents. It’s on account of their fatty membranes that these viruses are vulnerable to detergents and other soaps, and also to disinfectants (Please do not ingest or inject such substances as they are also bad for your own cells and also can mess up your body chemistry in ways that can be fatal). After attaching to an ACE 2 receptor, a SARS-CoV2 virus enters the cell by merging its fatty membrane with the membrane of the cell itself. In other words, the outside of the virus actually becomes part of the outside of the infected cell. In getting into the cell, the virus carries in a genome, a collection of genes, that we might say is analogous to a collection of files of photos that you keep on your phone.

Outside the realm of coronaviruses, there are some viruses that do carry in what can be called the Genetic Code. It’s because those viruses, unlike most, have their own reproductive machinery, and the Genetic Code is part of the reproductive machinery. We’ll unpack this idea a little later. First, however, a very important concept to keep in mind is that coronaviruses, and most other viruses, do not have their own reproductive machinery. Rather, they hijack the reproductive machinery of the cells that they infect, which means that they hijack the Genetic Code. They do this in order to make little baby viruses.

Let’s get into the machinery now, since it relates to the workings of a promising drug called remdesivir. The Genetic Code is included within the genome of YOUR cells. It is a set of genes, a set of instructions, that came into existence billions of years ago, instructions on how to build special types of RNA called transfer RNA, abbreviated as tRNA. Each type of tRNA is a piece of a codebook, because it connects a particular word in the language of DNA and RNA with a particular building block of proteins. If you change a gene that carries instructions for a tRNA, then you can change the Genetic Code, but this is NOT what a coronavirus does.

Now after a virus gets its genome into a cell that it infects, what it wants to do is to reproduce that genome so that instructions from that genome can then be used to make little baby viruses. As noted earlier, a minority of viruses do carry their own reproductive machinery, although coronaviruses do not. But whether with their machinery or with the machinery of the infected cell, the process of putting the viral genetic instructions into effect and building little baby viruses depends on a Genetic Code that has been part of the infected cell since long before the cell was infected.

In order to get itself reproduced by the infected cell’s machinery, what a coronavirus does carry within its genome is a gene with instructions for making a special protein. This special protein causes the reproductive machinery of the infected cell to make copies of the virus’s RNA. Normally, your cells make RNA from DNA messages, but they do not normally make RNA from RNA messages, so that special protein from the virus is key to the virus’s ability to reproduce. The special protein is a kind of enzyme, a biological molecule that enables a particular chemical reaction, in this case the production of viral RNA.

Now, remdesivir fits comes into the picture, because it is what doctors call a prodrug, a substance that becomes a drug after the body changes it a little bit. Once in your body, remdesivir turns into a molecule that looks very similar to one of the four building blocks of RNA. As a consequence, the special viral protein that makes RNA from RNA gets occupied making defective copies of the viral RNA. Manufactured by the pharmaceutical company Gilead Sciences, remdesivir was developed with hopes that it could treat Ebola virus, which is also a virus whose genetic material is in the form of RNA. Unfortunately, remdesivir did not prove very effective in people afflicted with Ebola, but the good news is that early results from clinical trials that Gilead is running with various medical centers suggest that remdesivir may reduce the severity and shorten the duration of COVID-19 symptoms.

In terms of pregnancy and breastfeeding, remdesivir represents a major unknown. The drug was given to pregnant women several years ago, but this was in settings of the outbreak of Ebola, notorious for killing upward of 50 percent of infected people. By comparison, the overwhelming number of people with COVID-19 do not die, especially among young adults, including pregnant women.  Presently, there are not enough data to know how the benefits of remdesivir weigh against any possible risks to a pregnant women, her fetus, or nursing infants. It is not even clear whether remdesivir passes into breast milk. According to the Gilead website, there have been an increasing number of requests to study remdesivir during pregnancy and breastfeeding.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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