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How about a nasal spray of Nanobodies, smaller faster and cheaper than antibodies?

 The “Aeronabs” are on the way?

Right now there are more biomedical research teams focused on one problem than at any point in history, and they are armed. This is Biotech’s Big Moment, and here’s just another potential game changer. The time line here is short, and the ability to scale it is large. The seige of 2020 will end one way or another, and we will gain a whole set of tools to use on other viruses too.

If the virus has a key to get into our cells, this is like making millions of decoy locks that stick to the keys and thus disable them.

What if we could coat our lungs with tiny particles that work like PPE against coronavirus? The aim here is that one nasal spray a day might stop the virus getting entry into our cells. At the moment, one team have this working in the lab already. They’ve created a kind of cut down mini antibody, and at this stage it sticks like glue to the viral spikes. It still needs to be tested in humans, and might yet fall in a hole. But it’s another example of the potential contained in molecular engineering on a scale like we’ve never done before. And we know something like this works in Camels, Alpacas and Llamas, because that’s where the inspiration came from — so it’s not entirely crazy.

Perhaps we’ll just “spray up” for holidays and parties?

The numbers involved in just this one research project are boggling. The team at UCSF started out with two billion different nanobodies and screened them down to nine that stick to the hot-money part of the Covid spikes — the key that opens a lock on the outside of your cells (called the ACE2 receptor). The idea is that any Sars Cov-2 viruses rolling around in your lungs will get coated with these little molecules and thus spin on uselessly for days afterwards, unable to use their keys to get in to your cells. The coated virus will get broken down eventually, as all viruses do when they can’t engage and use host machinery.

In short, if this works in people without any nasty side effects, it could change everything.

The process relies on finding a shape that is exactly right — that will only stick to the virus and then not let go. The research team added a clever modification. Because the virus spikes have three repeated “keys’ at the end of the spike, the team repeated and joined three nanobodies together in formation. When one binds, they all bind and it locks the spike up.

The abstract even refers to pico, nano and even a femto units.

And when they drew on the results of both modifications, linking three of the powerful mutated nanobodies together, the results were “off the charts,” said Walter. “It was so effective that it exceeded our ability to measure its potency.”

Back in 1989 researchers realized camel antibodies were like nothing they’d ever seen — much smaller, and that makes them much more stable, and easier to mass produce. We can genetically insert the right code into bacteria and use the microbial world as mass factories to generate billions of Aeronabs.

Derek Lowe writes about the discovery of these long ago, and how they blew away so many theories:

Camelids and Nanobodies

And with that, we shall now abruptly veer off into talking about camels, llamas, alpacas and their kin, because they have their own variety of antibody. No one knew that they had a different system going until 1989, when a student-run project at the Vrije Universiteit Brussel was trying to come up with a diagnostic test to check camels for trypanosome infection. They discovered that camel antibodies were. . .weird. Some of them were just like the ones above, but about 75% of the camel antibodies (and up to 50% in the New World species like llamas) have no light chains at all. They just have the variable parts of the heavy chain stuck directly onto the “base” constant region. Sharks and their relatives, as it turns out, have something similar going on with a different sort of base region, in what are clearly two different evolutionary events: at least 220 million years ago for the cartilaginous fish and 25 million years ago for the camelids. Both sets of animals seem to work just fine with their proprietary systems – before these discoveries, most immunologists would have said that that such modifications would be likely to cripple the antibody response, but not so.

 Vaccine testing is very slow in comparison. It aims to train a whole army — and then we have to check the results. This is vastly simpler, now we have the tools…

After WWII medical science conquered the world of bacteria with antibiotics. This then could be the start of the age of the Antivirals?

This video shows how complicated just the spike is, with the separate arms opening to activate the key. The new Aeronabs can join the three units at the top and stop them getting “armed and ready”.
Story sources:

Other things worth knowing

Is it a bioweapon?

Long term health effects and unrecorded “Excess” Covid deaths:
There are so many cheap ways to beat this virus:
Big picture policy — geopolitical

REFERENCES

Schoof et al (2020) An ultra-high affinity synthetic nanobody blocks SARS-CoV-2 infection by locking Spike into an inactive conformation, https://www.biorxiv.org/content/10.1101/2020.08.08.238469v1

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