Published on Mar 08, 2021

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, the chief medical officer at WebMD and you're watching Coronavirus in Context. Today I want to talk about tiny, little antibodies, what we're calling nanobodies, and how they might actually help us in the fight against COVID-19. So to help explain what this is all about, I've gone straight to an expert, Dr. Aashish Manglik. He is an Assistant Professor of Anesthesia and Pharmaceutical Chemistry at UCSF. Dr. Manglik, thanks for joining me.

AASHISH MANGLIK: Thanks for having me on.

JOHN WHYTE: Well, let's explain to the audience what are these nanobodies. And then I have to tell you, I was reading that the ones you're working on are from camels and llamas. Not what I would have expected hearing about this. So, can you explain what these nanobodies are?

AASHISH MANGLIK: Yeah. So you and I make antibodies. We make antibodies to fight off all kinds of infections. We're all hoping to get the coronavirus vaccine to help us make antibodies against the virus and help us prevent getting infected. But it turns out that animals like llamas or alpacas or camels make these tiny little antibodies that have been dubbed nanobodies. And the cool thing about these nanobodies is that they're very stable little proteins. And we've come up with a way of making these nanobodies that will attack the SARS virus and we think this can be a really interesting alternative, in addition on top of the vaccines that are kind of rolling out now.

JOHN WHYTE: Why do we think it's camels and llamas and animals like that as opposed to dogs or cows or birds? Why do you think it's llamas and camels?

AASHISH MANGLIK: Yeah. That's an interesting question. One of these questions about evolution about why things happen in evolution, it's always kind of hard to answer the big question of why. We know that it happened. And it turns out that it's not just, actually, camels and llama and alpaca that make as mini antibodies. Turns out that millions of years ago, completely independently sharks also evolved to make these kinds of mini antibodies. Now, whether these mini antibodies or nanobodies give these animals some better way of fighting off infections we can't really be sure, but it's clear that they make these unique kinds of antibodies and we think that they're really useful for a variety of purposes.

JOHN WHYTE: Now you mentioned proteins, and really this is a study of proteins in a way. And you talked about proteins are kind of like LEGOs, but they're like jelly LEGOs.

[LAUGHS]

I mean, they are constantly changing. So in order to get protection, you need to have binding to have them come together. So how do you address this in terms of these nanobodies?

AASHISH MANGLIK: Yeah. So think for a minute, how does a virus actually get inside your body? There has to be some little hook or attaching-- something that allows it to attach onto your cell. And that's been mapped in beautiful resolution. We know that there's these proteins on the SARS virus called spike proteins. But this protein, this spike protein which has become so famous now, isn't just a simple little grappling hook. It's moving and changing its shape. And the way in which it changes its shape is what it uses in order to attach to our cells in the first place.

So one of the ways that we can prevent the virus from actually attaching to cells is to basically strait-jacket this movement. To prevent it from doing this business. And the way that we do this is making antibodies as mini antibodies-- nanobodies-- to fix the shape of the spike protein and prevent it from having this jello or wiggly motion that it normally needs to get inside cells.

JOHN WHYTE: Now, where are we on trials for this?

AASHISH MANGLIK: So still pretty early days. We know that, in a test tube, that these nanobodies work really effectively at destroying the virus. So once one of these little nanobodies that we've engineered binds to the virus, it completely prevents the virus' ability to get inside cells. In a test tube works really well. We've done some studies in animals now that also show that this works. But now we're at the stage where we're trying to find the right steps forward to basically bring this into patients for patient testing. And we're in the midst of that phase right now.

JOHN WHYTE: So you're not actually in phase two and phase three trials or anything like that. Is that correct?

AASHISH MANGLIK: Yeah, so this is relatively earlier phase than much of the research that's already entering patients or is poised to, for example, to be approved by the FDA to start attacking the virus.

JOHN WHYTE: Now, would this be for prevention or, like, a vaccine or is it really for treatment? Where do you see this fitting in?

AASHISH MANGLIK: So this is where it's really unique. I think it kind of fits a very unique niche, both for the current pandemic and likely for future respiratory pandemics, either a future influenza pandemic or a future coronavirus pandemic. On the one hand, we think that an approach like this could be great for treating people who just learned that they're infected. So let's say you just got a test done, you found out that you're positive for the virus. We tell most people, hey, go home and if you get really sick come back to the hospital. But a treatment like this that you could give yourself-- for example, squirt up your nose or inhale-- could perhaps decrease your odds of really getting quite sick. Especially if you're high risk. So that's one approach.

JOHN WHYTE: I wanted to ask you that because you have mentioned that this could be over the counter or self-administered. So it wouldn't be an infusion like monoclonal antibodies, correct? And it wouldn't be an injection like the current vaccines. Why can it be through a mist or some type of other mechanism other than our traditional ones that we think about?

AASHISH MANGLIK: Yeah. So that's really why we started this project in the first place because there are a lot of groups-- a lot of industry groups or other academic groups-- that were bee-lining ahead trying to make antibodies against the virus. And what we've seen is that those molecules work great in a test tube and also in animals, but the big challenge for these antibodies has been that because patients need to come to an infusion center to get them, the logistics of getting that all worked out is pretty challenging.

So the premise that we had for our approach is that these little mini antibodies are so stable that one could directly just give themselves one of these reagents directly in their nose. Now whether it can be over the counter or not, that's a much more complicated issue. But the critical thing is that our approach could be self-administered by people and wouldn't require someone to come into an infusion center or a hospital in the first place.

JOHN WHYTE: So we're in the midst of a pandemic. We want as many effective therapies as soon as we can. How much of this, Dr. Manglik, is sci-fi and how much is we might be able to have this in several months or a year? What's your sense of timing?

AASHISH MANGLIK: Yeah. Well, we're pushing very hard to take the sci-fi into real science or application. We think that it's very likely that we could get it into patients and probably even have some results within the year. Now whether that really ends up mattering for where we are in the pandemic right now, what happens with these variants that come out, all of that kind of stuff, and how well the vaccines continue to work against the variants, all of that is such a dynamic thing that we're not sure. But certainly for the next pandemic, which is likely to happen with a different coronavirus or influenza virus, we think a similar approach could be really effective, especially if people get out the gate really rapidly developing these kinds of reagents.

JOHN WHYTE: Do we have any examples in medicine currently where we've used nanobodies?

AASHISH MANGLIK: Great question. There's one clinically approved drug for a completely different type of disease, for a bleeding disorder. And that's a nanobody that's actually also given through the blood. There's one other company that had previously brought an inhaled nanobody for a respiratory disease to patients and they ended up getting to about phase two trials. They saw some effectiveness, but the kind of disease they were treating, the only way they could treat it is relatively late in the course of disease so they didn't have as much clinical benefit as anticipated. That's part of the reason why we think this approach would have far more benefit if we target patients very early in the course of disease.

JOHN WHYTE: Well this is exciting. We're going to have to check in with you in a few months and see where you are. I want to thank you for taking the time to help explain this new technology that we may be able to use, if not for this pandemic, for the next one that comes along. Dr. Manglik, thank you.

AASHISH MANGLIK: Thanks for having me on, John.

JOHN WHYTE: And if you have more questions about nanobodies or questions in general about coronavirus, drop us a line. You can email them to me at [email protected] or post them on Twitter, Instagram, and Facebook Thanks for watching everyone.

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