[DR. DUTCH] Essentially if you ask me what do we need to do to reopen the country now, we really only have a few good options: one would be a really good antiviral.

[GEORGE] An antiviral is a drug that fights a viral infection.

We do have them but we don't have that many and we certainly don't have one that cures COVID-19.

Why not?

I dunno.

So I called a bunch of virologists to ask them what was taking so long.

[DR. RACANIELLO] Viruses are so intertwined with the cells which they need to replicate, they use so many cell functions, that it's hard to target a viral function that does not impact the cell and so you don't have side effects.

[GEORGE] Let's take a moment to compare viruses to bacteria.

Bacteria live and reproduce outside your cells so it's easier to target them with a lot less collateral damage but viruses reproduce literally inside your cells.

So what does that mean for drugs?

Is it harder to develop an antiviral than an anti something else like an antibacterial agent?

[DR. DUTCH] it is much tremendously more difficult, and there's probably a lot of reasons for that, one of the prime ones is that viruses grow inside our cells.

[GEORGE] So fighting a bacterial infection is kindof like pulling olives off of a pizza.

Pretty easy.

Fighting a viral infection is like trying to get them out of this calzone.

It's a lot harder to kill the olives without also damaging the calzone or at least it would be if this one didn't have gigantic holes in it.

So it's really hard to fight the virus without also hurting your cells, but it's not impossible.

To stop the virus from replicating you have to know exactly how it replicates, and that brings us to this new coronavirus.

When the virus gets into your cells it releases its genome, part of which gets translated into an enzyme called an RNA dependent RNA polymerase.

This enzyme is critical because it copies the viral genome.

Without that enzyme the virus cannot replicate.

Three important things to know about this RNA dependent RNA polymerase: first if you could somehow take out this enzyme you could theoretically stop the infection; second, [DR. DUTCH] the RNA dependent RNA polymerase is unique to these viruses [GEORGE] What that means is that the virus has a target that your cells don't have.

So if you could shut down this enzyme you could prevent the virus from replicating without messing up your own cellular reactions; and third, this RNA dependent RNA polymerase is an enzyme [DR. RACANIELLO] Those are great targets because they typically have a small active site that's, what we say druggable you can design a small molecule to bind into it and inhibit it.

[GEORGE] So it's actually not too hard to make a molecule that will inhibit an enzyme and a test tube or let's say in a small used jar of tomato paste, but then you have to actually turn it into a drug that would go into people.

[DR. RACANIELLO] You know just having a compound that inactivates infections not good enough, you have to make sure it doesn't have side effects, right, and you have to do that in animals.

You have to make sure if it's taken orally it's going to get into the blood, and you have to make sure it's potent, so you may have to do multiple cycles of iterative chemistry to modify your original hit so that it has all these good properties and that can take a long time.

[GEORGE] Now let's say you do find the perfect molecule, you can't just start handing out prescriptions left and right.

What you have to actually do is give the drug in small doses to small numbers of people to see if it's safe, and then you can do larger trials to see if the drug actually works.

All that testing normally takes months or longer sometimes years.

[DR. OFFIT] So for our vaccine, for example, that was a 70,000 infant, prospective, placebo controlled, four year, 11 country, 350 million dollar trial.

to prove that the vaccine was when you claimed it to be.

[GEORGE] He was talking about a vaccine trial but the same principle applies for any drug that you're trying to bring to market.

So does that mean that we have to wait four years for a seventy thousand person, prospective, placebo-controlled, double-blind trial for a SARS-CoV-2 antiviral to hit the market?

Not necessarily.

If you have an antiviral that's already been approved for, let's say HIV, or if you have an antiviral that's been tested for some other disease and found not to work, you could take that antiviral and immediately start testing it in people to see if it helps fight COVID-19.

[DR. RACANIELLO] Whenever you take a drug so far as to be in people there's always a hope that you can revive it for something else and sometimes drugs can affect more than one virus even if you developed it for Ebola, so people have said let's test it.

[GEORGE] He's talking about a drug that you might actually have heard of it's called remdesivir.

[LISA JARVIS] So just to back up, this is a drug that was invented during the 2014 Ebola outbreak in West Africa.

[DR DUTCH] Remdesivir was developed against Ebola, but it works against the RNA dependent RNA polymerase, and the coronaviruses have a very similar polymerase [GEORGE] So they did all the safety and efficacy studies of this drug back in the mid 2010s.

As far as the FDA is concerned it is safe to go into people.

Unfortunately, it didn't work against Ebola, but that doesn't mean we can't try it for COVID-19.

[DR. RACANIELLO] So people have said let's test it.

[GEORGE] So that's where this particular drug is right now.

It was tested against Ebola, it didn't work but it's being tested for COVID-19, and in fact you may or may not see something in the news right at this very moment that I'm recording this.

It's not by any means the only drug we're testing we are literally throwing the kitchen sink at this thing right now.

LITERALLY.

There's another drug in Japan that also targets that same enzyme we've been talking about: the RNA dependent RNA polymerase.

There are drugs that are thought to target completely different parts of the viral replication cycle, for example, the antimalarials that have been in the news a lot lately.

There are antibody drugs that you could develop from people who have recovered.

So if you go on clinicaltrials.gov right now, and search for interventional trials on COVID-19, you'll get more than 600 results.

So why don't we have wonder drugs against viruses?

Well it turns out we're working on it.

Normally that process would take months, years, decades sometimes, but now the global research community is doing that whole kitchen sink thing, you know?

This, right here, kitchen sink.

We here at reactions, as well as our friends over at C&EN, are keeping a close eye on where things are in the pipeline.

For updates as we know them keep your eye on the description, or you know both eyes.

And again let's keep that big picture in mind.

Ideally you'd want a vaccine so that people don't get COVID-19 in the first place, but if they do get it you also want a really good antiviral.

Until we have both of those things keeping your distance is best.

Howdy, neighbor!

Oh, a puppy!