- [William] So here's a coronavirus story
that starts like a lame joke.
In late February, just before
everything started shutting down,
three virologists walk into a conference room.
- [Nat] It was one of the last days the three
of us were allowed in a conference room together,
actually on campus.
And you know we were just,
you know we were really lamenting the fact
that here we go again, right?
- [William] The three of them, Nat, Ralph and Mark,
they're frustrated 'cause
they're starring down a very familiar situation.
Nat says.
- [Nat] Here comes another epidemic.
Here comes another pandemic, as it turned out,
and we don't have anything.
You know, there's no drug ready.
- [William] He's talking about the SARS
and MERS outbreaks.
They were caused by coronaviruses
a lot like this one.
But all the research that followed never turned up
a knock out coronavirus drug,
one that could help us fight this new virus,
but also the next one to appear.
- [Nat] Instead we saw the scramble starting.
We were scrambling ourselves,
trying to create antiviral drugs in real time,
and that's now how the drug development process works.
- [William] But there in the conference room
they hash out a different approach,
one that could lead to more future proof drugs.
No more scrambling,
no more reacting.
It just meant flipping
their virus fighting strategy on its head.
- [Nat] But what we realized is
you could turn that concept around.
SARS, SARS2 and MERS, right?
So these are viruses that are in the same family,
but there's still a lot of variation.
- This is real life Nat Moorman.
He works at UNC Chapel Hill
with colleagues Ralph Baric
and Mark Heise.
We talked to Nat months
after that day in the conference room,
and he told us more about why SARS and MERS
didn't give us a big leg up on COVID.
- There's a lot of differences between those viruses
in the sequence of their actual genomes,
and also in the sequences of the proteins
that they encode.
- [William] Viruses are wildly diverse.
They differ in their sizes and shape,
how they enter our cells,
how they mature and replicate.
The problem is those things are all targets for drugs,
a drug that targets a specific part
of one might not work on another.
Also, if that one part mutates the drug could break.
- [Nat] It just takes one change
to make that drug not work.
- Now some drugs can work on multiple viruses.
Remdesivir is one that's currently in use against COVID.
It messes up viral RNA replication.
And in the lab it looks to be effective
against SARS, MERS and COVID.
The FDA has only authorized it for severe cases.
And it's effect is modest.
Still, it's a start.
But Nat's team is chasing a different strategy.
They started a program called READDI
to take on new viral threats like this one.
And instead of hunting around old viruses for new targets,
they're looking at us.
- [Nat] What we realized is
you could turn that concept around.
- [William] The idea is this.
Viruses can't reproduce on their own,
they need a host cell
and the machinery inside to replicate
and mature and spread.
The trick is our machinery,
our cells can respond to drugs too.
- [Nat] So when a virus infects a cell,
it turns on or turns up a lot
of cellular processes.
If you can reverse that change back to the level
of activity that was present in the uninfected cell,
you could inhibit the virus replication.
And even if you don't completely stop it,
you can give your immune system time to respond
and help clear the virus.
- It's an idea that could make a big difference
if we can understand how this virus changes us.
- So we're generating that data
for SARS2 right now.
What are those changes?
- If it works, this approach could be future proof
in ways that others just aren't.
Since these drugs focus on our cells,
they're less dependent on the specific features of viruses.
So mutations might be less of a problem.
And the approach could be effective
against viruses that don't exist yet.
The next coronavirus might look
or act very differently,
but it might co-opt our cells in similar ways,
so it might be vulnerable to the same drugs.
- So the idea is to take that approach,
use it in a proactive manner
to go ahead and develop those drugs now
so that we have them ready on the shelf
before the next epidemic or pandemic arrives.
- Now this is not a new idea,
it's actually how lots of drugs work.
If you have arthritis
or high blood pressure
or a headache, you can take drugs
that work on your own cells.
But Nat says antivirals that work this way
have gotten more attention post COVID.
It's one of those ideas that could really go places.
- Well, it's good to dream big.
Our ultimate goal,
you know, our aspirational goal,
would be to find a truly broad spectrum compound
that would inhibit all these different families of viruses.
Now, did we think that was the most likely outcome?
No, but it's a good goal.
- Nat's team isn't taking that big a swing.
They're focused on coronaviruses, flaviviruses
and alphaviruses, three families
with high pandemic potential.
But what'll it take to make those big discoveries?
Partly that depends on whether
there's interest in the research
after this pandemic is over.
Historically, that's been a struggle.
Just look at SARS and MERS.
- [Nat] They were scary things.
Everybody recognized the potential
devastation they could cause,
but they were contained.
And people move on from those things.
A non-virologist, if you remind them,
will remember it happened.
But the answer you typically hear is
yeah, but that wasn't really
that big of a deal,
not realizing how close we really were to that
being that big of a deal.
Life moved on
and so did the funding and the interest.
- Of course COVID is that big a deal.
So hopefully the next wave of research will be too.
Hey everyone, as the pandemic grows
and evolves, we wanna hear from you
about what kinds of COVID stories you're interested in.
So let us know in the comments,
and day to day to stay up to date,
head over to theverge.com.
Thanks for watching.