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One of my Brainstormings (a mesh of interconected ideas that didn't solidify into a concrete story yet) had an interesting sideplot:

One of the main characters, Cephit, is a young gold dragon with an axe to grind on another main character for indirectly (and accidentally) almost getting her father killed in an incident involving fire giants. But since family-friendly is still turned on, Cephit's father survived (mostly). He can move his limbs well, do normal stuff and is perfectly fine mentally (as in no brain injuries) but has little to no stamina, making him incapable of extended work or fulfilling his role as a leader for the rest of his life.

The problem is that these are dragons, the result of Anon's Project Kars that aimed to create the perfect creatures. They have the same regenerative ability as Axolotls and an immune system that incorporates nanomachines and gets regular updates from a gigantic, external pathogen database (think of GNU/Linux security patches and virus-definition databases).

Obviously, mechanical stuff are out of question which leaves as with bio-weapons and yet another inspection by the FBI.

So, how would a weapon be able to permanently cripple and only cripple a dragon?

Stamina is one thing, ability to regenerate is another. On top of that, both regeneration and a supreme immune system are things that require energy.

Let's take a human for example. Michael Phelps is popularly quoted as having a caloric intake of 12,000 daily calories. That is not true; according to him, he only eats up to 10,000, most likely 8,000 though.

Let me put it in lay terms. People thought his intake was six times the average for a human adult, but he confessed to only eating four to five times the average.

Back to the discussion at hand: you have to eat a lot to be a gold medalist. Even if you don't want to take part in the Olympic Games and all you want is to get buff, you're going to need to eat a lot. A 25-30 year-old, ~70kg (around 140 pounds) sedentary man might need only 1600-2000 calories per day, but professional soccer players would go anywhere from 4,000 to 6,000. Some quick googling says that for another sport, football, some athletes have caloric intakes of up to 9,000 calories per day.

Now the tricky parts. First: just eating like an athlete doesn't make you an athlete. If you eat 9,000 calories a day without much exercise, you are probably too obese to move out of your bed. A regular person going from 2,000 to 9,000 overnight would most likely die due to liver or heart failure in a few weeks.

Second, and this is the most important point of my answer: this goes the other way around! If you exercise like an athlete but you don't get the calories you need from food, you're going to get them from your body. Once there's no sugar in your blood you'll start eating through your fat reserves, but once those are gone your body will tear muscle for energy. You will be clinically undernourished.

Your dragon might be in that condition due to his immune system. If the immune system has an energetic cost of 30,000 calories per day and the dragon is only eating 28,000, he will starve and become weak.

In other words: your dragon might not exercise, but he has the caloric budget of an exercising dragon. If he isn't able to get enough nourishment, he won't have the energy to do much.

As to how to get to that point through injury: maybe he got hit with something biological, which his immune system can keep in check but not really cure. For example, a batch of nanobots that reproduce too fast for the healing nanobots to completely eliminate. Or perhaps he got dragon cancer. The healing factor can't really kill all cancerous cells because they are genetically too similar to the healthy cells, so they can only fix the damage being caused by the cancer.

I'm thinking a nanomachine infection could be the answer.

Foreign nanomachines have infiltrated into his system, and are both self-replicating and are tuned for something else - another species, perhaps(?). As a result, your dragon has the equivalent of Glandular Fever in humans - a (usually) low-grade infection that has a large effect on stamina and endurance.

These aren't being fixed by the immune system updates because the cause hasn't been discovered / detected yet. Also, depending on where you want to go with this, the cause of this nanomachine infection could be damage to existing nanomachines causing misprogramming; nanomachines from another species that can survive in the dragon's system (like how flu jumps from birds and/or pigs to humans); or a deliberately planted nanomachine designed to debilitate a dragon in this way.

He hacked the update server for the nanomachines server and pushed an update that made them attack this specific dragons lungs/heart as identified by genome. And he did it so incompetently that he didn't deactivate the regenerative function for said dragon so the nanomachines are constantly both destroying and rebuilding those organs. That (or the incompetent hacking) triggered the servers anti-virus protection and it sealed off all manual access and is only accepting automatic updates from nanomachines themselves, therefore nobody can fix the issue.

You mentioned nanobots and security patches. From a pure CS perspective, no software is secure. Yes, nanobots are hardware, but there is code in even the simplest hardware. If a device/weapon somehow corrupted much of the code that fixes the dragon, this could be (at the base level) what happened to the dragon's healing abilities.

Another thing you might want to keep in mind is that living creatures are made of cells, and cells can only multiply a certain number of times, and not all life-forms can actually grow back limbs and body parts. In addition to this, no computer is perfectly functional forever - I think one estimate I read was that your computer will only works at peak performance for 2 years, after which it slows down just because of age. So the virus/weapon that is used on these dragons could compromise the code or hardware that counters the effects of straight up aging to a point.

Also - what's the best way to clear data in a computer? Use a hammer. Now, some hardware can be fixed, but perhaps the technology used in the dragons' healing mechanisms aren't repairable. That's why you can survive, but the full scale of the healing factor and stamina will never be recovered for that reason.

Now what does this weapon look like? It could be used physically, like straight up stabbing a dragon in the right place with a blade covered with nanobots built to reprogram dragons, or it could be a signal that randomly or specifically corrupts dragons enough to defeat them (not kill, but at least take them out).

Basically, what you're looking for is a type of virus that is transmitted in some way. I'll try to add to this answer if I can do so later.

Temporal cripple

The new member is regenerated, but the new member is new. This means that the new muscles are weak, and the new member is ineffective until the dragon has had time to train them.

Lack of nutrients

You may have all of the nanobots in the world; if you do not have calcium enough to build the bones the resulting bones may end being weak, malformed or both. Lose too much of your body and the rest of it will simply do not have enough supply of minerals/proteins to regenerate the lost member as it should.

Cummulative errors

Nanobots are not perfect, and sometimes mistakes happen. If the member to rebuild is small enough, most of the time those errors will be insignificant enough to be barely noticeable (and if sometimes the error is noticeable, the dragon may simply cut the member and start the process again).

But if the member is big enough, those mistakes begin to add and will practically always affect the viability of the new tissues. In those cases cutting down the crippled member to have it grown again is of no use, since the number of mistakes is guaranted to be high enough that the new member will always be malformed.

The weapon "damages" the wound and stops the nanites

The nanites work ok when you slice through a dragon, as they flow to the blood and, at the same time that they stop bleeding, they start reconstructing the body.

But your weapon not only cuts the flesh but it also affects the remaining flesh; perhaps it is a flaming sword that burns the flesh of the wound (or petrifies it, or whatever). The nanites just cannot penetrate that layer of dead tissue to begin the reconstruction of the member.

Drinking and mistaken identity.

The fire giant has a number of Magmin warriors visiting on the occasion of the encounter. They are being entertained in the next room by dancers and libation of (whatever Magmins drink) some indeterminate hot sticky fluid. They speak of their magma pools with longing and of their war with Magma Dragons with hatred and considerable boasting of feats of moxie and daring in battle they get rather rowdy and worked-up about the whole thing.

The drink runs out, the Magmins emerge seeking a Magmin equivalent of a kebab shop or burger joint. They spy the dragon and being blind-drunk immediately their ire is up mistaking it for a Magma Dragon. They attack, their primary weapon being teeth and their primary interest being fresh liver, they latch on, bite off chunks of flesh and then whip out the liver whole and munch away, until finally they are stopped. Everyone is really sorry for the mistake in the morning and of course the Nano-machines sealed the wound and stopped all bleeding.

No liver means much less by way of glycogen stores, there's some energy stored in the muscles, but continued exertion requires a liver - sure the nano-machines can clean the toxins from the blood and such, but they can't store the necessary energy to provide true stamina.