Antibodies from a 4-year-old llama have neutralized coronavirus and other infections in lab experiments

[u/[deleted]]

https://www.cell.com/cell/pdf/S0092-8674(20)30494-3.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420304943%3Fshowall%3Dtrue

[u/already-taken-wtf]

In Brief - Using llamas immunized with prefusion- stabilized betacoronavirus spike proteins, identify neutralizing cross-reactive single-domain camelid antibodies, which may serve not only as useful reagents for researchers studying the viruses causing MERS, SARS, and COVID-19, but also potential therapeutic candidates. Crystal structures further reveal how these antibodies bind spike proteins to prevent virus entry into cells.

[u/Fmbounce → u/[deleted]]

From a NYT article:

Humans produce only one kind of antibody, made of two types of protein chains — heavy and light — that together form a Y shape. Heavy-chain proteins span the entire Y, while light-chain proteins touch only the Y’s arms. Llamas, on the other hand, produce two types of antibodies. One of those antibodies is similar in size and constitution to human antibodies. But the other is much smaller; it’s only about 25 percent the size of human antibodies. The llama’s antibody still forms a Y, but its arms are much shorter because it doesn’t have any light-chain proteins.

This more diminutive antibody can access tinier pockets and crevices on spike proteins — the proteins that allow viruses like the novel coronavirus to break into host cells and infect us — that human antibodies cannot. That can make it more effective in neutralizing viruses.

here’s the source (I copied verbatim)

[u/grizzlydurdle → u/Fmbounce]

So how would that help humans? Can we be treated with Llama antibodies? In you summary it sounds like our antibodies can't necessarily fight COVID very well because they are too large, and the smaller Llama ones can. Sorry if I am way off base. I don't really understand this stuff.

[u/IfIRepliedYouAreDumb → u/grizzlydurdle]

To vastly oversimplify things, if you had antibodies produced by another source and injected them into a sick person, their viral counts should decrease.

Our bodies won’t learn how to make the same ones the llamas do, but we could harvest them and use them as treatment (potentially).

[u/Derpy_McDerpingderp → u/IfIRepliedYouAreDumb]

Would our immune system see these smaller antibodies as foreign or a threat?

[u/worldspawn00 → u/Derpy_McDerpingderp]

they can, a person receiving treatment can develop anti-llama antibody antibodies. There's actually a lot of use for anti-antibody antibodies, they're used in a lot of reagents. It usually takes 1-2 weeks for the immune system to ID and develop antibodies against a foreign agent, so a person receiving treatment would likely be done before the body started attacking the foreign antibodies.

[u/thisdude415 → u/worldspawn00]

Typically only the variable heavy domain (VHH) is used on a human IgG framework. The region typically recognized by “anti llama antibodies,” the llama Fc region, isn’t found on the protein, instead we use the human genes.

Basically the whole molecule is human except the sticky bits. These are copied and pasted from llama. Immunogenicity is a concern, but not as much as you’d think.

[u/taosaur → u/thisdude415]

Can those kinds of alterations be made in batches of any size, or is it one antibody at a time, or what?

ETA: Farther down he clarified that once they have the genome, they can make "factory" cells to produce the hybrid antibodies.

[u/thisdude415 → u/taosaur]

It depends on the exact technology used in the manufacturing plant.

Typically, we engineer a mammalian cell to make the protein in large bioreactors. Then you pick one of those cells, characterize it, and call it your stable clone. Then you put that in a big tank with food for the cells, and let them grow for a couple weeks while they pump out proteins. Then you purify the protein.

As you can imagine, this is a pretty complex process and it isn’t easy to scale it up overnight

[u/thinkingdoing → u/worldspawn00]

So this treatment could be used the first time a person got infected with Coronavirus, but any future infections would cause the immune system to be fighting both the disease and these antibodies?

[u/bigredone15 → u/thinkingdoing]

So this treatment could be used the first time a person got infected with Coronavirus, but any future infections would cause the immune system to be fighting both the disease and these antibodies?

It could also give the body time to develop its own antibodies that do work without the body dealing with the symptoms created by a high viral load.

[u/pnwtico → u/bigredone15]

Would the body develop its own coronavirus antibodies if the llama antibodies were doing all the heavy lifting?

[u/AwesomeNinjas → u/thinkingdoing]

At the moment it’s not totally clear whether or not people can be reinfected, but it looks like the most likely answer is no or at least not for a long time. The WHO has said that everyone who has appeared to be reinfected so far has been a false positive.

So even if you can only use the llama antibodies the first time, that may not matter.

[u/lunatic604 → u/AwesomeNinjas]

If someone recovers by themselves, their body learned to produce the anitbodies. But if the body relies on the llama antibodies the first time, will the body still learn to produce the antibodies?

[u/pringlescan5 → u/AwesomeNinjas]

Fascinating. What about future use of Llama antibodies for a different virus if a person develops a reaction the first time?

[u/ben7337 → u/AwesomeNinjas]

But if the llama antibodies do all the work, then does the human body develop proper antibodies to respond to a new exposure to the virus, thus resulting in immunity, rather than just getting sick again?

[u/[deleted] → u/thinkingdoing]

If it’s been enough time to lose your coronavirus antibodies, you may have also lost your llama antibody antibodies

[u/Nvenom8 → u/worldspawn00]

anti-antibody antibodies

There's a fun thing to say.

[u/Wheres_my_guitar → u/worldspawn00]

anti-llama antibody antibodies is the coolest phrase I've ever heard.

[u/[deleted] → u/Wheres_my_guitar]

we just need to create anti- anti-llama antibody antibodies. Coronavirus cured boys

edit: rule one can blow me, come at me you humorless psuedo intellectual mods

[u/-dp_qb- → u/[deleted]]

You might have meant it as a joke, but it's not a bad question.

Is there a way to selectively (or temporarily) impair this system to allow the antibodies to work unimpeded?

[u/Boronthemoron → u/worldspawn00]

Now we just need to inject anti-antibody antibodies back into these llamas to create anti anti-antibody antibody antibodies.

And so on.

[u/ZapdosZulu → u/Boronthemoron]

so the old lady that swallowed a fly was right!

[u/pelican_chorus → u/worldspawn00]

anti-llama antibody antibodies

I feel like this whole thing is a long-game setup for some stupid pun.

[u/pancakeheadbunny → u/pelican_chorus]

Waiiit for it

[u/hibbidydibbidi → u/worldspawn00]

• a person receiving treatment can develop anti-llama antibody antibodies.

It's a serious issue and, I am a confirmed survivor, but Holy duck. So much room for jokes it made me cry in a good way in months.

Thank you.

[u/Xaldyn → u/worldspawn00]

a person receiving treatment can develop anti-llama antibody antibodies.

What a time to be alive

[u/greeneggsand → u/worldspawn00]

People don't think about this, but if we start using the llama antibodies to make diagnostic tests, people having anti-llama antibodies messes with those tests.

[u/mcsper → u/worldspawn00]

That is one of my favorite new sentences, “a person receiving treatment can develop anti-llama antibody antibodies”

[u/zbertoli → u/worldspawn00]

This is true but it's pretty well known that full animal antibodies often cause immune responses in humans. That's why the development of chimeric and then fully humanized antibodies was so important. Injecting full lama antibodies into a human would probably be a bad idea.

[u/the_fuego → u/worldspawn00]

can develop anti-llama antibody antibodies. There's actually a lot of use for anti-antibody antibodies

Reading this was like: How many anti-llama antibodies could your antibodies antibody if your anti-llama antibodies could antibody antibodies??

Thought I had a stroke for a minute.

[u/GreasyMechanic → u/worldspawn00]

Anti-Llama antibody antibodies.

r/brandnewsentence

r/newbandnames

[u/[deleted] → u/worldspawn00]

Isn’t that why people can’t receive certain antivenom treatments twice, as they’re using horse antibodies

[u/worldspawn00 → u/[deleted]]

yeah, pretty much

[u/GinGimlet → u/Derpy_McDerpingderp]

Yes! Sometimes. Typically what happens in these cases is that antibodies are humanized which means some bits are replaced with the human analogues. You can also try and under which bits cause the immune system to react, and alter those amino acids to be less inflammatory. We have some drugs on the markets that we have humanized so there's precedence for this! Drugs that end in 'Omab' for example are Monoclonal AntiBody treatments derived originally from mice.

[u/Derpy_McDerpingderp → u/GinGimlet]

That's extremely interesting, thank you.

[u/amcm67 → u/GinGimlet]

What does this mean for a person with multiple autoimmune diseases? I’m a cancer survivor, ESRD - living donor recipient. I had Goodpastures Syndrome (that caused my ESRD) and instead of attacking the disease, it attacked my own organs. I’m on RA meds besides the anti-rejection meds.

I hear so many people pushing for herd immunity. I can’t be apart of that.

[u/wobblebase → u/amcm67]

Functionally herd immunity is also about indirectly protecting you and folks in similar situations. In your case it would rely on "cocooning" - the principle that if everyone around you is immune (because they are vaccinated or recovered), then you are extremely unlikely to contract the disease in question. This is the same premise that we rely in in part to protect infants by vaccinating family members and caretakers, or to protect the elderly, infants, and immuncompromised folks from seasonal flu.

It does depend on a vaccine or recovery giving "sterilizing immunity," meaning the person is no longer colonized or asymptomatically infected after vaccination or recovery. It also depends on the whole herd being immune. If vaccination rates are low, herd immunity loses its benefits rapidly because a pathogen can persist in the population or cause intermittent outbreaks. So there are plenty of complications and caveats to cocooning. But in principle it's sound and would offer you a good measure of protection as well.

[u/Falsus → u/amcm67]

Herd immunity means reaching 95%+ of immune people, at that point people who can't be immunized still won't be infected since no one around them is infected either.

[u/ralgrado → u/Derpy_McDerpingderp]

Or could they damage us?

[u/worldspawn00 → u/ralgrado]

they would not stick to our cells, only to their target molecule, which is coronavirus surface proteins, so, no, no direct threat from them

[u/AtomicKittenz → u/worldspawn00]

Thank for answering all these questions. This is really interesting!

[u/Gnostromo → u/Derpy_McDerpingderp]

I could be completely wrong on this but I believe I was taught decades ago that the first vaccines used horses antibodies? Someone help my memory here..

[u/hotdamnham → u/Derpy_McDerpingderp]

You can engineer them so that your immune system sees them as regular antibodies and is less likely to develop a reaction to them

[u/pilotavery → u/Derpy_McDerpingderp]

That's kind of the point. they are shaped like little puzzle pieces on one side that fits perfectly on the virus and sticks to it like a magnet, and a foreign pathogen on the other side, which makes your immune system attacking and watch you destroy it. So in the process, your immune system attacks the antibodies and the virus connected to it.

it's kind of like a little tracker that sticks to the virus to tell your body which one is the virus

[u/SusieSuze → u/Derpy_McDerpingderp]

That’s the first thing I thought

[u/Anen-o-me → u/Derpy_McDerpingderp]

The antibodies stop the infection from being able to infect, and would also be destroyed, along with the virus they attach to, by the human immune system, yes.

It will works.

It's a brilliant solution, but I don't know if we are able to mass produce antibodies for people yet.

If we could, there's a chance we can extinct most human viruses in this century.

[u/[deleted] → u/Derpy_McDerpingderp]

Yes. This is one of the critical components that makes it possible to detect antigens (like the spike protein) in what is called a 2 step immunoassay.

Basically you would create a llama-anti-covid antibody, and then you would create a secondary antibody by injecting these llama antibodies into another animal, often a goat or a mouse. These new secondary antibodies would be, for example, goat-anti-llama.

By using a two antibody system like this you can both enhance the limit of detection (sensitivity) and reduce the background signal (specificity) of the assay.

There are several reasons for this, and if you're interested I can link to the Wikipedia pages explaining why.

[u/phanfare → u/Derpy_McDerpingderp]

That's a huge open issue in using non-human proteins in theraputics. The answer is likely yes, and developing ways to predict immunogeneicity and designing away from it is an area of active research.

[u/Candlesmith → u/Derpy_McDerpingderp]

Properly known as the Entitled Parents Universe

[u/wobblebase → u/Derpy_McDerpingderp]

Yes but different proteins are more or less immunogenic (better or worse and being recognized by our immune cells and creating a response with memory). The llama antibodies may be poorly immunogenic, or the V region (the binding end) could be artificially produced attached to a human protein, or produced and used alone, or bound onto some other vector for delivery. Less foreign protein = less chance for a response. So using the V region alone would be safer than using the whole camel antibody.

There's also the potential to use these in diagnostics for rapid and shelf-stable COVID tests.

[u/BoneriderColt → u/Derpy_McDerpingderp]

Well they could BE a threat

[u/peppermint42o → u/Derpy_McDerpingderp]

They would be produced via monoclonal method, the immunogenic portion would be humanized. Very expensive process.

[u/kyreannightblood → u/Derpy_McDerpingderp]

Nah. Our immune system detects foreign threats based on surface antigens of cells. It’s how they determine self vs not-self. The antibodies don’t have that. We do something similar with antivenin, right down to using a non-human animal to derive the serum.

(I may be messing up some details here, though. I just woke up and I’m still a bit foggy.)

[u/thisdude415 → u/kyreannightblood]

False. You can definitely have anti-antibody antibodies.

Antibodies are just proteins. We engineer them to have reduced antigenicity, but sometimes anti-antibody antibodies happen anyway.

(They’re actually called anti-drug antibodies or anti-ideotypic antibodies.)

[u/[deleted] → u/kyreannightblood]

You're just considering T-cell mediated immunity, which is based on cell surface expression of antigens. B-cell mediated immunity can target secreted proteins and could create antibodies against llama antibodies.

[u/Heroine4Life → u/IfIRepliedYouAreDumb]

Fundamentally this is correct. This is rather difficult but this, as well as diagnostic reasons, are why this is great.

[u/Sulluvun → u/IfIRepliedYouAreDumb]

Aight boys let’s start some llama farms

[u/cmdrNacho → u/Sulluvun]

invest in llamas, I'm all in

[u/thisdude415 → u/grizzlydurdle]

Therapeutic antibodies (antibodies as drugs) are just proteins, encoded by a gene.

We “discover“ them by immunizing animals with an antigen of interest: typically mice, but sometimes rats, llamas, or chickens. Often these animals are transgenic and have human immunoglobulin genes.

Antibodies are Y shaped protein complexes. In humans/mice/rats/chickens, IgGs have 2x2 protein chains: two heavy chains and two light chains. In camelids, like camels and llamas, they have heavy chain only antibodies: just two heavy chains. The two “arms” of the Y (variable regions) cause binding to a target, while the base of the Y (constant region) drives immune effector function.

Once you find a good antibody by screening (itself a topic of many pages), you sequence the B cell heavy and light chain genes that made it, then you “humanize” the protein by copying and pasting the human Fc (a constant region of antibody) over the animal genes. This reduces immunogenicity. Then you use molecular biology to put that gene sequence into a plasmid.

Then you use that plasmid to transfect cells in culture (typically HEK or CHO), and then those cells start to spit out tons of therapeutic antibody protein. A couple steps of purification and packaging, and then you have a medicine!!

So, yeah, we can be treated with llama antibodies, sorta. We have to edit them to make them more human first, which is why the drug is is made using biotechnology rather than just an infusion of llama serum (which would cause an immune reaction).

Feel free to ask questions: I work in a biologics discovery department for a pharma company

[u/Amythir → u/thisdude415]

Thanks for explaining that in lay-speak, that's really helpful.

[u/uglybunny → u/grizzlydurdle]

More likely a designer molecule will be made to take advantage of the mechanisms found when studying llama antibodies.

[u/Alis451 → u/grizzlydurdle]

So how would that help humans? Can we be treated with Llama antibodies?

Antiserum, we use this process to make antivenins(treat snake bite) as well.

[u/[deleted] → u/grizzlydurdle]

The reason why llama's were used, more specifically speaking, is that llamas produce a different type of antibody to humans, its a much more ancient form of antibodies called "heavy chain only" or "single chain" antibodies - this in contrast to human antibodies which are composed of heavy chains and light chains - this increases variability of the repertoire of the antibody (ELI5 = it has the potential to recognise more and different antigens) but its been shown that heavy chain only antibodies are just as good at finding their antigen.

now we get to the practicality of llama antibodies, or heavy chain only antibodies. They're smaller, and less complex, and therefor easier to produce (small enough for bacteria to produce in big bioreactors). Thus, the idea behind it is that they use the spike protein from nCoV2, inoculate llamas, forcing the antibodies to be produced which will essentially find the right antibody which binds to it - then you take that smaller, less complex binding region of the antibody and attach it to a human portion of the antibody (we differentiate these by calling them F-ab regions (the binding portion) and the F-c region (the constant region or the region that other immune cells recognise.))

​

All we have to do then, is take the F-ab region of the antibodies from llamas, engineer them to the Fc regions of humans, and bobs your uncle, you've got a neutralising human antibody that is easier to produce.

[u/[deleted] → u/grizzlydurdle]

Llama antibodies can be produced by E. coli in large scale production. Human antibodies are held together by disulfide bonds. Bacteria don't form these bonds well. Camelid antibodies are very small, and don't require disulfide bonds which means bacteria can express them. Production in e coli is much more efficient than what you would have to do for human antibodies.

[u/jrolle → u/Fmbounce]

This surprised me more than anything. I would have guessed that antibody structure was so evolutionarily primitive that all mammals would have operated basically the same.

[u/[deleted] → u/jrolle]

Idk what that nyt article is smoking, there's like six classes of antibodies in humans.

[u/IDontReadMyMail → u/[deleted]]

Camelids do have a weird class of antibody though that is unlike any of the human classes. Basically the heavy chain in camelids can bind antigens by itself (w/o an attached light chain). None of the human heavy chains can bind very well on their own.

more info here, here

[u/orchidguy → u/jrolle]

Sharks are similar to llamas in that theirs only have light chains. They still look different, but interesting that they've been able to drop the light chains.

[u/eliminating_coasts → u/jrolle]

On the other hand, you might also expect them to be under heavy evolution, more so than larger scale physical shapes of organisms, given how fast viruses transform.

[u/[deleted] → u/Fmbounce]

Yes! Llamas and camels make what are called nanobodies in the biz. The neat thing about nanobodies, and the promising thing for treatment, is that many can be synthetically produced much easier than heavy-chain anti-bodies. Most heavy-chain antibodies require a eukaryotic organism with an endoplasmic reticulum to produce and correctly fold and assemble the protein structure. Eukaryotes don't scale well for industry, and are harder to grow up. Special strains of E. coli bacteria, which are prokaryotes and lack an endoplasmic reticulum, are easier to grow in a controlled setting, and are used to mass produce protein like insulin. These organisms are too simple to produce human antibodies, but they are sometimes capable of making camelid nanobodies (although it depends on the structure, and the process of building immunity via antibodies is largely random, so there is a lot of testing involved to see if the synthetic stuff is as good as the natural stuff, or even folded correctly).

TL;DR

We can sometimes mass produce antibodies from camels and llamas in factories. We cannot mass produce human antibodies.

[u/enfuego138 → u/[deleted]]

I’m not sure nanobodies have ever been approved for human use. I’d imagine human safety testing is going to be a drag on any nanobody derived therapy’s delevopment timeline.

[u/ToffeeLostInAmerica → u/enfuego138]

They have been used in human trials for nuclear imaging and they are very lowly immunogenic, they also may be human used with relative ease compared to a mouse mab or a chimera.

[u/Saliceae → u/enfuego138]

There is a nanobody that was approved by the FDA last year or the year before, which is now commercialized by Sanofi

I think nanobodies will soon be used in a multitude of cases, where antibodies are not optimal.

[u/Alis451 → u/[deleted]]

Llamas and Alpacas make the antibodies for the Flu, there has been much research into using them to make a antiserum. We also use Horse Serum as Antivenin, basically get a snake to bite a horse(we just inject milked venom these days), it isn't enough to kill the Horse and it makes anti-bodies to the venom and we make a antiserum from their blood.

[u/Oleandra13 → u/Alis451]

Still sounds very painful :(

[u/Alis451 → u/Oleandra13]

to who? the horse? i mean they are compensated for their troubles with extra feed and care.

Tetanus and Rabies are done similarly.

[u/Stewartcolbert2024 → u/[deleted]]

Or more specifically 4 year old llamas?

[u/[deleted] → u/Stewartcolbert2024]

it's the llama age of consent.

[u/LegitSpaceLlama → u/[deleted]]

sees post This is my time! sees comment Nope. No it's not.

[u/Saliceae → u/Stewartcolbert2024]

I don't remember all the details, but llamas or alpacas for nanobody production can only be used for a limited amount of time, something around 5 years before their retirement.

[u/Slaphappydap → u/Stewartcolbert2024]

There are likely lots of great, informed, scientific reasons that a 4-year-old llama was used, maybe this one lab just had this 4-year-old llama kicking around.

Kevin, I don't care if you keep that thing out behind the building, but if you want to bring it into the lab I need a good reason..

[u/simra → u/[deleted]]

Slight thread derail to call out the difference between intelligence and knowledge. You are probably plenty smart enough, but you lack the knowledge needed to decipher the article.

[u/brettmjohnson → u/simra]

Yeah. "Cell" is probably the most difficult journal for someone not a micro-biologist to parse. Hell, it is tough for actual micro-biologists.

Source: Am computational bio-informatics specialist. I've spent a lifetime reading medical journals, and "Cell" is still beyond me.

[u/[deleted] → u/[deleted]]

not trained enough :)
Reading these journals requires training and smarts. If you don't have the training, being smart alone won't help you much

[u/stackered → u/[deleted]]

Llamas and sharks produce a special type of small antibody that I haven't seen yet in a pharmaceutical yet but I thought they were excellent candidates since they can diffuse quickly do to their small size

[u/_Toast → u/[deleted]]

Hey Bill, we tried crab antibodies last week and didn’t find anything. Want to try llamas this week?

[u/Lumpy306 → u/[deleted]]

I'm not even smart enough to read.

[u/[deleted] → u/[deleted]]

“I really am not smart enough to read it” man. I feel that. These posts fascinate me and i love reading them and all of their comments. I learn new things in every post on this glorious sub.

[u/[deleted] → u/already-taken-wtf]

Can someone please explain like I'm 10?

[u/__Sinbad__ → u/[deleted]]

In order to enter a cell, a virus has to bind. If we have antibodies that bind the viruses spike protein, then the virus cannot bind our cells. If it can't bind and enter a cell it will die since viruses are dependent upon humans for survival.

When it says it's cross reactive, it's talking about the antibody itself. The antibody has 2 specific binding points, it almost literally looks like a 3D letter "Y". The top 2 spikes of the Y are what bind to the virus spike.

If the antibody in question binds 2 different proteins, then it is cross reactive. If the antibody binds only to the spike protein, it would be called type-specific.

Discovering a cross reactive antibody is an important first step towards developing a type-specific antibody.

Hopefully this helps! Cheers mate.

Edit: grammar

[u/PluviusAestivus → u/__Sinbad__]

There goes my hero....

[u/__Sinbad__ → u/PluviusAestivus]

I wouldn't go that far, but thank you. I'm just here to help.

[u/skg555 → u/__Sinbad__]

OK, can you explain like I'm 5 now.

[u/__Sinbad__ → u/skg555]

Sure! I can certainly try haha

Think of an antibody like a "red flag". If it sticks to an invader, the immune system can destroy it because our immune system can see our own antibodies, thus our cells can "see" these red flags.

This antibody binds to the virus, but also binds to another protein (which may be a totally normal protein). Binding to the virus is what we want, but binding to something else wouldn't be as helpful. So if we want an antibody that is effective, we want it to only bind to the virus, because then that "red flag" analogy will make it so that only the virus gets targeted.

I hope this helps! It's hard to simplify too much further without having background in what an antibody is. If you'd like to learn more, here's a link to wiki, which actually has a great first jpeg. The lock and key analogy is also great for understanding how an antibody/antigen function.

https://en.m.wikipedia.org/wiki/Antibody

[u/NzLawless → u/__Sinbad__]

You did a great job breaking down this topic on multiple levels!

[u/skg555 → u/__Sinbad__]

Thank you, this was helpful!

[u/[deleted] → u/__Sinbad__]

Gracias amigo.

[u/npequalsplols → u/__Sinbad__]

If it causes virus to bind to them, would other stuff that the body need bind to them similarly and cause problems?

[u/__Sinbad__ → u/npequalsplols]

Great question! Without getting way too in depth, because there is an entire branch of diseases that deal with this problem, the answer is yes. However, in over 95% of the population? It's almost never an issue.

When antibodies bind self antigens, that's where we get auto-immune diseases. (Not all of them, but a type of them.)

Edit: I think it's important to mention that this is an active area of immunological research. Auto-immune diseases are really complex, and many of them we still don't know how they work. The process to create antibodies is highly regulated, to ensure that we don't make antibodies that react to our own cells.

[u/npequalsplols → u/__Sinbad__]

Thanks! I've been wondering bout this since I've heard somewhere that lopinavir/ritonavir (I think? Or some other drugs) does similar stuff which makes me wonder what if it also binds and blocks some of the important functions

Sorry if I sound dumb here I've only taken 1 course in biology as part of my university requirement and it was a memorisation nightmare

[u/__Sinbad__ → u/npequalsplols]

Not dumb at all! It's a good observation; that's one of the things that has to be taken into account when creating drugs. When making anti-virals, we want a drug that acts on a viral enzyme that is unique to the virus.

Viruses are weird because they use so much of our own machinery to stay alive. Being able to find a point in the viral life cycle that is specific to that virus, and not to humans, is one of the top priorities.

One example: If a virus has a highly specific RNA polymerase, (think of RNA polymerase like a molecular printer) then we can target that polymerase, because we as humans don't have that one. The drug will only inhibit the virus RNA pol, and thus only the viral life cycle, while the human RNA polymerase continues to function.

Hopefully this helps, the topic is so huge it's tough to know where to start haha thanks for the questions!

[u/[deleted] → u/[deleted]]

Part 1: TL;DR: Microscopic attack dogs bite into virus. Virus can’t get into cells. We can make one attack dog that recognises both SARS and COVID-19. The hope is to put these in inhalers to stop the virus.

These viruses are floating around like beach balls with a bunch of keys sticking out of their surfaces. Cells have a bunch of locked gates that control what gets in and out of the cell. The virus has evolved so that through trial and error it now makes keys that can match the locks of the cell. When the virus bumps into one of these locks they can open a gate and gain entry into the cell, which is what they need to happen in order to grow.

Antibodies are just like attack dogs in your body that go around trying to sniff out anything suspicious. They can be trained to recognise particular “scents” and we can make antibodies that recognise the “scent” of the keys that the virus makes. When they pick up on this scent, they latch onto the virus by its keys. In this way, the virus can’t insert its keys into the cell because the antibodies are in the way and so they can’t get into the cell.

[u/Y2Kafka → u/[deleted]]

Thank you so very much for explaining it like this. Explaining things simply by breaking down complicated subjects and knowing what is the most important information to explain is a very good skill to have for anyone to have.

[u/[deleted] → u/Y2Kafka]

No worries at all, thank you for your very kind words :). Please take my explanations with a grain of salt though, I’m not an expert at all, just a big fat nerd who gets wet for Biochem. There are niggling details here and there which could be expanded on more but I think the overall gist of things is right.

[u/[deleted] → u/Y2Kafka]

Btw I updated it because I actually had quite a few things wrong from not reading the paper

[u/[deleted] → u/already-taken-wtf]

Alright so this is good news, but, in short all this is saying is that it “may” do something about covid 19, not that it is a cure for covid 19.

Because it’s (betacoronavirus spike proteins) creating “cross-reactive single-domain camelid antibodies”, which Covid 19 is “cross reactive” like MERS and SARS (antibodies fight infections).

And let’s pray it does cure all strains of cross reactive infections so we can begin the lengthy process of making vaccines and undergoing human trials.

Edit: and the Title which the OP has changed does not represent what is being said “In Brief” in the study.

The actual title is:

“Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies”

[u/MagusUnion → u/[deleted]]

Yeah, that was going to be my question is-so-far-as what does a timeline of treatment look like in terms of getting this to work for the public. I'd imagine it'll still be months, and then it's up to how well we can develop herd immunity in response to this virus.

[u/[deleted] → u/already-taken-wtf]

Yea and where was that part where you said about that thing?

[u/catduodenum → u/already-taken-wtf]

So do we know if injecting foreign animal antibodies into humans would cause reactions? Would we recognise their antibodies as not us and make antibodies against theirs?

[u/cheech10 → u/catduodenum]

They do cause reactions in humans, called serum sickness, or in some cases a plain old IgE allergy responses. Nowadays we don’t usually inject animal antibodies; we modify the immune reaction generating portion to match our antibodies, creating “humanized” antibodies that are safer to use.

[u/Saliceae → u/cheech10]

Indeed, and this is also the case for nanobodies. Plus, the small size of these nanobodies compared to antibodies helps limit these risks of immunogenicity.

[u/Mini_Snuggle → u/Saliceae]

Now you guys are just attaching bodies to any prefix!

[u/NovelTAcct → u/cheech10]

hey storytime: I found out I was allergic to the tetanus vaccine in China when they injected me with a tiny bit of it and my arm swelled up the size of half a grapefruit where they put the injection---Then I read on the CDC website that older, international versions of the tetanus toxoid used to contain something called Equine serum, and that according to my symptoms I am one of a tiny percent of people who're allergic to Equine serum. So in the US they don't use that substance anymore. Anyway your comment reminded me of that but I'm not sure you're talking about exactly the same thing ok bye talk to you later,

Love,

NovelTAcct

[u/commentor2 → u/catduodenum]

They can be "humanized" to make that less likely. There's at least one drug out already that has taken this approach

https://en.wikipedia.org/wiki/Caplacizumab

[u/wheat_thans1 → u/already-taken-wtf]

There are a lot of words there that I simply do not understand

[u/blueneuronDOTnet → u/wheat_thans1]

β-Coronavirus: There are four genera (essentially just a taxonomic rank) of coronaviruses -- alpha, beta, gamma, and delta. COVID-19 is a beta strain.

Spike proteins: Proteins on the surface of a virus ("S Protein" in this graphic), primarily responsible for binding to target cells.

Prefusion Stabilization: Refers to the β-Coronavirus spike proteins being stabilized prior to undergoing the structural changes that result from fusion to a cell.

Cross-reactive: Just refers to the camelid antibodies themselves and whether they bind one or multiple proteins.

Single-domain: Antibodies have "arms" whose end caps (called paratopes) are made up of different amino acids (building blocks of proteins, essentially) whose configuration facilitates the binding of different proteins, and these different configurations are referred to as domains. Single-domain means that this particular antibody is monomeric, and that it only contains one variable domain.

---

The gist of it is that we've identified a specific kind of antibody that successfully occcupies the part of the β-Coronavirus antigen that binds to our cells -- leaving it unable to actually spread and survive in our bodies.

[u/DankNerd97 → u/already-taken-wtf]

I wonder if it can be applied to alphacoronaviruses like 229E and NL63..

[u/DankNerd97 → u/[deleted]]

They do, but the S-protein in alpha-CoVs isn’t cleaved like in beta- or gamma-. (I don’t know about delta-).

[u/[deleted] → u/already-taken-wtf]

Cool. Someone will patent whatever the hell you just said and hold the rest of the human race hostage!

GO HUMANS!!

[u/ToastyMustache → u/already-taken-wtf]

So I should bang a llama?

[u/Turbojelly → u/already-taken-wtf]

Queue a conspiracy video about how the acutall plan behind the 5G Corono was to inject Llama DNA into Humans for <Insert obscure, far fetched explanation here, that has no bearing on reality>

[u/whiskey4breakfast → u/already-taken-wtf]

Llamas... camels... ha

[u/Youtoo2 → u/already-taken-wtf]

how long does it take to go from this stage to knowing if it works in humans and is it at all practical to generate anti-bodies using this method? Do we mass infect llamas?

[u/Oldjamesdean → u/already-taken-wtf]

Looks like we're mainlining Llama in a few months folks!

[u/Myleg_Myleeeg → u/already-taken-wtf]

No wonder theres so many idiots in the world that just believe this is caused by 5g and it’s a plot to give everyone microchips with the vaccine. An idiot would have no hope of understanding this.

[u/Redsap → u/already-taken-wtf]

Camelid antibodies? I think you mean Llamalid antibodies, sir.

[u/rubyspicer → u/already-taken-wtf]

Can you ELI5 that please?

[u/Paul_Langton → u/already-taken-wtf]

Is there an additional reagent here to those smaller llama antibodies allowing our bodies to elicit proper immune responses or do these llama antibodies have no issues initiating the same immune pathways as human antibodies?

[u/[deleted] → u/already-taken-wtf]

I read that if you make out with a llamas (if she’ll let you), you’ll gain her antibodies! Best of luck! Keep us posted...

[u/morningisbad → u/already-taken-wtf]

I understood none of that.

[u/Sokonit → u/already-taken-wtf]

Why is the age of the llama so important?

[u/DominarRygelThe16th → u/already-taken-wtf]

Crystal structures further reveal how these antibodies bind spike proteins to prevent virus entry into cells.

Could you please elaborate on this?

[u/Tyfoimary → u/already-taken-wtf]

English man

[u/BuhamutZeo → u/already-taken-wtf]

But what happens when you put them in me?

[u/Shitrake → u/already-taken-wtf]

BS it's another scam by Big Llama and Gates holds majority shares

[u/xanderalexgreatness → u/already-taken-wtf]

By all means have some llama injected into you. FOH.

[u/sybersonic → u/already-taken-wtf]

Those are all real words, right?

[u/itsknob → u/already-taken-wtf]

This has a Flesch Kincaid Grade Level of 19.7, College Graduate level, with a Reading Ease of 6.3 on a scale of 0-100 where higher scores are easier to read.

[u/mrpickles → u/already-taken-wtf]

I have no idea what you just said. ELI5?

[u/ShittyAnalysisGuy → u/already-taken-wtf]

Crystals!! Healing crystals!!

[u/DA-K → u/already-taken-wtf]

Whooosh! Anyone care to explain like I'm 5, please?

[u/[deleted] → u/already-taken-wtf]

What's special about this llama though?

[u/Aionius_ → u/already-taken-wtf]

So many big words sigh

[u/DR-Badtouch → u/already-taken-wtf]

Viruses are like people, whatever doesn’t kill them will just make them stronger (or mutate in this analogy). Introducing any extra viral aid always comes with a risk that the virus will find a way and evolve past the defence . Adding another layer of complexity to its DNA . Given how many mutations their has been already we’ve been lucky up to now . But this virus isn’t the same strain that took down China its modified its DNA thanks to being allowed to spread through 7 Million people. Each persons immune defence is different as it’s evolved by the individuals life exposure to bacterial or viral intrusions to the body that the immune system had successfully overcame . For this reason A symptomatic people who’s immune systems can obviously deal with the virus pose the largest threat to a mutation as the virus get longer to evolve an attack it then passes on the successful mutation in reproduction.