Podcast Host, David Ryan:

Hello, and welcome to the podcast. In the coming weeks, we'll be learning more about coronavirus. Not just about the virus itself, but of the response to the global pandemic that has shut down cities, forced people into their homes and started a race to find effective treatments and therapeutics. In today's episode, we'll talk to Dr. Ivan Martinez. He's a virologist at West Virginia University and an associate professor in the school of medicine, and also works at the WVU Cancer Institute. He studies how viruses infiltrate and take control of healthy cells. He's also interested in viruses that are made of RNA instead of DNA, a category that includes the novel coronavirus. We'll talk about how viruses work, what treatments are being prepared and what goes into making a vaccine as well as much more.

Podcast Host, David Ryan:

Science may seem slow, but it turns out something might be even slower. The novel Coronavirus itself. Sure, we've seen it spread quickly across the globe. And yes, symptoms of COVID-19 can come on suddenly, but the virus is slow to evolve. And according to Dr. Ivan Martinez, a virologist at WVU, that reluctance to change is a good thing for us. Martinez is an associate professor in the school of medicine's Department of Microbiology Immunology and Cell Biology. And he's part of the WVU Cancer Institute.

Dr. Ivan Martinez:

We have to be careful when we compare coronaviruses versus influenza viruses. Coronaviruses have actually a low mutational rate so they don't mutate very fast compared to influenza viruses that cause the flu. The difference is this, so coronaviruses, you might know that coronaviruses comes and infects the cell and the virus in the moment that infect the cell, eject their genome into the cell. And the genome is going to be copied by an enzyme, but a protein that the virus has. This enzyme copy the genome of the virus, but this enzymes is not very accurate and sometimes make mistakes. So these mistakes create mutations in the virus. So these happen with all viruses. All viruses have these enzymes or proteins that copy their genome. And some of them are not very good, but that's coronaviruses and other viruses, but influenza viruses are quite different. Influenza viruses actually, instead of having just one genome inside the virus, they have eight fragments that actually create the genome of influenza, and that gives them a huge advantage compared to coronaviruses.

Dr. Ivan Martinez:

Because imagine if you have two different influenza viruses that infect the same cell at the same time. And now these eight pieces of one influenza, mix with the other eight pieces for the other influenza viruses. And now they are going to resort this and in the next generation of viruses, they're going to be completely different. And that's the ability and the advantage that influenza viruses have to mutate very fast from one generation to the other, you can create a completely new virus and that's why it's been so hard to find vaccines against influenza compared to coronaviruses that I'm sure that it is the same mutational rate that other viruses have that is kind of low is good for us because that means that we can find, hopefully soon, a vaccine against these viruses, against coronaviruses, and this specific one COVID-19 and be successful.

Podcast Host, David Ryan:

The fact that the novel coronavirus mutates so slowly might make it easier to develop and administer a COVID-19 vaccine. Think about it, every year vaccine developers have to come up with a new flu vaccine to target the flu strains that they predict will dominate the season. A more consistent virus like this one might be easier to kill with a single vaccine.

Dr. Ivan Martinez:

People have to be, of course, careful going out and interacting with other people, but don't be completely afraid. So we have to be careful. We have to of course, wash our hands, take our social distance, and do whatever scientists and the government is telling us to do to protect ourselves, protect our family and protect the community.

Dr. Ivan Martinez:

But again, we don't have to be paranoid about this because this is not the first time that the world is dealing with a pandemic. The last real pandemic we had was in 1918 with Spanish influenza that killed millions and millions of people around the world. But at the end of the day, as the world survive and move on. So we believe these virus, this pandemic with this coronavirus specifically, there's potentially two things that could happen before we develop a good vaccine against it.

Dr. Ivan Martinez:

One is that these will become just endemic infections, meaning that we have already other coronaviruses in the population that they are actually causing between 10 to 30% of the common colds that we all have. So maybe these COVID-19, or also known as SARS-CoV-2 will become another endemic coronavirus that we have to deal with it every year until we have a vaccine. That was one scenario. The other scenario will be that we have to deal with it only seasonally that will come during the winter. And it'll become more like a bad flu season. So now it will become more like a coronavirus. And again, we will need to take our precautions.

Dr. Ivan Martinez:

But at the end of the day, I'm pretty sure that we will prevail and we will move on and we have to go back to our normal life as much as we can.

Podcast Host, David Ryan:

When we do find a vaccine, it might not be right to say it will kill COVID-19 because you can't kill what isn't alive. You may have heard about how long the coronavirus can "live on a cardboard box or shopping cart handle." But technically the virus is not a living thing ever. Unlike bacteria, they cannot reproduce on their own. And that's something all living things have to be able to do.

Dr. Ivan Martinez:

So viruses actually, is really nothing else other than a small infectious agent or an inactive macromolecule that technically speaking, is not alive. Is not alive like a bacteria or us ourselves. So viruses, they are not considered alive because they cannot make more viruses just by themselves. They need to infect a life cell, meaning a host and then steal their machinery, steal all their molecules inside a cell to make more viruses.

Dr. Ivan Martinez:

And that's why viruses are very different from bacteria, in that sense. They are considered not alive. And also they steal machinery from the inside of cells they are infecting. Now, there's also a big difference between sizes. If you look at sizes, viruses can go from 20 nanometers to 450 nanometers. So that maybe doesn't tell you too much, but if you have the diameter of a hair, human hair, you can probably put like 200 to 300 viruses together in that hair. And viruses are definitely smaller than bacteria. So we talking about 10 to a hundred times smaller than a bacteria in size.

Podcast Host, David Ryan:

Viruses may be simple. They may not even be alive, but they've been around a lot longer than we have. In fact, by the time humans arrived on the scene, about 200,000 years ago, viruses had already been doing their thing, infecting lizards and lemurs, trees and termites, for millions of years.

Dr. Ivan Martinez:

They probably evolve with life when life started in this planet. There've been there forever. We don't know exactly where they come from, but there are a lot of theories what they could potentially come from. But in any case, that's why they have that ability in the sense that because they're so evolved so independently with life in general, that they have the ability to go in and steal all these machinery. They already know that it's there. So it's really a very fascinating mystery because we don't know exactly what was first, the chicken or the egg.

Dr. Ivan Martinez:

So was first life on earth and then viruses came from that life? Or viruses were first and then something happened that created something more sophisticated, like a life cell. There are a lot of theories. There's even from the 1960s, people were talking about an RNA world where the very first signs of life in this planet was based on RNA and if that's true, maybe viruses was one of the first things that remember resemble some of the things that is alive, but it's not.

Podcast Host, David Ryan:

So maybe it should come as no surprise that viruses are as resilient and diverse as they are. They got a huge headstart. But just how diverse our viruses really? Well consider the virus that causes COVID-19. It's part of the coronavirus family, which got its name because under a microscope, a coronavirus looks a little bit like a spiky crown. It's a vast family. In terms of scale, don't just imagine a Thanksgiving dinner table, imagine a family reunion that takes over a park and spills into the parking lot.

Dr. Ivan Martinez:

They are hundreds if not thousands of coronaviruses effecting different animals. There are several studies showing that they are coronaviruses that can affect pigs and cows and cats and bats. And there are probably thousands of them. [inaudible 00:10:24] we know that COVID-19 most likely came from was from bats. And the last literature that I checked actually says that there are probably around a thousand coronaviruses already been found in bats. Now from all that, a huge amount of viruses are limiting other organisms that could potentially jump to human. That is called a spill over. That's when a virus that is in an animal actually is able to infect humans. There's only been actually seven coronaviruses as far as we know that infect humans. So from that seven, four coronaviruses are the ones like I mentioned before, are both between 10 to 30% of the causes of common cold in humans are actually caused by these coronaviruses and being with us.

Dr. Ivan Martinez:

Actually the first two coronaviruses were discovered in the 1960s and the other two were discovered around 2003, 2004. Then around 2002, that's when the SARS, the original SARS, the Severe Acute Respiratory Syndrome virus came and that was the fifth coronaviruses that we know that affect humans. Then in 2012, that's when the Middle East Respiratory Syndrome virus came, MERS, came in 2012. And that was the sixth virus that we know of infections. And finally, of course, the one we are dealing right now that is COVID-19, also known as SARS-CoV-2 appeared in 2019.

Podcast Host, David Ryan:

And that's just the coronavirus family. If you start to consider other virus families, the scale becomes staggering. Millions of virus types have permeated every ecosystem on earth. There are rhinoviruses which cause the common cold and influenza viruses, which cause the flu. There are viruses that are infect humans and viruses that infect other animals and plants and insects and even bacteria.

Podcast Host, David Ryan:

Some viruses have DNA the way we do. In fact about 8% of your own DNA right now originated from ancient viruses and got combined with the human genome as our species evolved 8%, but other viruses don't have any DNA at all. Instead their genomes are made of RNA.

Dr. Ivan Martinez:

So if we talk about RNA in general, when they teach you your classes of molecular biology when you go to high school or even college, they, for many, many decades, people always thought that RNA was just kind of like a transitional molecule. We always believed that was kind of, it was called the dogma biology, the dogma of molecular biology.

Dr. Ivan Martinez:

That means that our information, our genetic information is in the DNA. And then RNA was some sort of a messenger molecule that was taking this information from DNA to another part in the cell to make proteins. And that was really the only function at that time, people believed that was it. Of course now we know that is not true. RNA is very important. Not only for that type of job inside the cell to send information from one place to another, but now we know that RNA has so many other functions, so many, so many is from, they have the ability to work like an enzyme. They have a catalytic activity, they can be like a genome. Like we've been talking about coronaviruses. Coronavirus is one of these many, many viruses that their genome is not DNA, it's actually RNA.

Dr. Ivan Martinez:

So RNA is a very flexible molecule that can not only contain genetic information, but also can have a function as an enzyme, as a messenger, and as a regulator of other RNAs and other proteins. So now we start to understand the importance of RNA, not only in any type of organisms and human diseases, but also in a viral infections.

Podcast Host, David Ryan:

The virus that causes COVID-19 is an RNA virus and its own RNA may end up playing an important part in our fight against it. Scientists are looking into using parts of the virus's RNA as ingredients in a COVID-19 vaccine.

Dr. Ivan Martinez:

These vaccines that we are trying to develop, or people are trying to build right now, there is like a super fast track type of vaccines. It is a very interesting type of technology they're using right now to develop these vaccines as fast as they can. So when people said we would not going to have a vaccine in a year, year and a half, people think that, oh my God, that's a long time. In reality, that's a very fast developing of vaccine.

Dr. Ivan Martinez:

Developing a type of vaccine, like I said, takes many, many years. This is a completely different type of technology they're using. They actually, they're talking about RNA. They use fragments of RNA from the virus, some of these industries, there's some of these places they're trying to develop the vaccine. They're using fragments of this RNA from the virus and put them artificially in cells. So they can actually make proteins of the virus without having the whole virus entirely. So it's very safe and they're trying to find it as accurate as possible. So they can develop a very unique antibodies, a vaccine that could develop antibodies specifically for the virus. And that way you can administrate these vaccines very fast. And it doesn't take that long compared to a traditional way of making vaccines. That, like I said, it takes too many, many years.

Podcast Host, David Ryan:

Another vaccine candidate that has been gaining attention in the news was developed by the University of Oxford in England. That vaccine is a little different and is already entering advanced trials of its own.

Dr. Ivan Martinez:

So they make like a Frankenstein virus that has a little piece of the COV-19. And this is where sometimes other vaccines work like Ebola vaccine. They put a fragment of the virus, in this case, COV-19 in another virus like [inaudible 00:16:42] virus. And you put it in animals or humans and potentially develop antibodies against that fragment of COVID-19. The other virus is more like a vehicle that is helping these other proteins to be inside a cell. So you kind of combine two different viruses and get the protection for one of them.

Podcast Host, David Ryan:

And the work doesn't stop there. Researchers aren't just exploring ways to help the immune system recognize and react to a coronavirus invasion. They're also developing a treatment to keep the immune system from overreacting to the virus because when that happens, the immune system can start attacking healthy cells, as well as the sick ones, blood vessels can leak, blood pressure can drop, and organs can fail.

Dr. Ivan Martinez:

What kind of therapies really we can develop there's just so many people working on that. I will say there's more than 20 different compounds around the world that are trying to test, do clinical trials with them and hopefully some of them will work. One of them actually that I was reading that looks very promising, I think comes from the University of Washington Seattle, and a group I think mostly in Canada, they are trying to develop... So the way you were describing how the virus attaches to the cell. So coronaviruses, the name coronavirus means crown because they have these very big, when you look in the microscope, they look like a crown around the wires. So they have these called peplomers or spikes that are very big. And these spikes are kind of like a key that is going to recognize a receptor in the cell.

Dr. Ivan Martinez:

And these receptors called, ACE-2. Now we know that. These ACE-2 receptor in the cell, the virus recognized it, attached to it. And now this is going to help in the absorption of the virus inside the cell. So the problem with these ACE-2 receptor and the virus is that ACE-2 expression is we have a lot of ACE-2 receptors in our cells in our lungs.

Dr. Ivan Martinez:

And these receptors important actually to don't have a overreact immune response. When we have that, the immune response in our lungs are acute. Okay. The moment that the virus attached to this receptor and goes inside a cell, the virus actually stop and absorb these receptors, and now these receptors are not out anymore. And because they're not out any more then this over reaction and over-inflammation of the lungs and that's why a lot of people are suffering from this.

Dr. Ivan Martinez:

So there's actually a company trying to develop these kind of artificial receptors that you can put artificially in hopefully they can, are able to mass produce and then put them in the lungs of people. So the virus, first of all, the virus instead of binding to the receptor of the cell, they will bind to these a mock receptor that is just kind of floating around. And now you kind of inactivate the ability of the virus to attach to your cells. And also these receptors will help to keep the immune system not overreacting. So I think that kind of technology is very promising and I hope they can achieve a good therapeutic.

Podcast Host, David Ryan:

Even though it can look like we are all on our own, retreating into our homes and socially distancing ourselves, as well as countries keeping borders shut and trying to prevent the spread of the virus. The scientific community has rallied together with an aggressive spirit of collaboration and cooperation as the fight to find a vaccine progresses.

Dr. Ivan Martinez:

I think right now is amazing that having these pandemic, even though of course, everybody's at home and have to be protected is just been amazing how the scientific community around the world is being together. In my generation it's the time I see something like this, that the entire scientific community, biomedical science community is together. We are all releasing every single thing that we discover, releasing for free. Everybody can see it as fast as they can.

Dr. Ivan Martinez:

There's been a lot of groups together and not only the United States, but around the world, trying to solve these pandemic. And even from WVU. We have a lot of people in WVU, they've been collaborating, helping each other. All this support comes all the way from the President Gee, from the Dean Clay Marsh, and also from the Dean of Research in the School of Medicine, Dr. Laura Gibson. They're been giving us a lot of support for this collaboration and trying to help with one way or the other to develop tests for coronavirus here in the state. But also, like I said around the world is just being very uplifting feeling that this is helping us to be united.

Podcast Host, David Ryan:

If you're interested in learning more about West Virginia University's response to the COVID-19 pandemic, visit coronavirus.wvu.edu, follow us on social at WVU Health on Facebook, Twitter, and Instagram. Make sure you subscribe to this podcast on your favorite podcast app to get the latest episodes as they're released.