The business seats on a plane make more money than the economy seats. However, there aren't lines where you can fill a whole plane of business: economy is there mostly to fill up space

I agree it is a fixed cost, but the initial cost is expensive by itself before we consider the cost for maintenance. Also 5x for economy is really expensive, I highly doubt that many customers would want this 380 experience for 5x of econ. Airbus 380 is ideal for long distance, then 5*800 from NY to Asia would be too damn expensive: then why not first-class on non-380?

That’s part of the reason US based airlines don’t fly to most gulf region airports anymore.

1) they could essentially justify a lightly loaded economy section due to Business / First passengers (I’ve done several cheap mileage runs before where I had multiple rows to myself in economy). When those $$$$ passengers switched to the nicer Emirates/Etihad/etc flights, they lost that marginal advantage.

2) on top of #1, another major factor is that Etihad/Emirates/etc are heavily subsidized by their national governments. Due to this, the slot fees were much cheaper for them than US based airlines further reducing any money to be made on those segments by US based airlines.

The end result of the above is that now you have to use an alliance partner + connection to get from US to the Middle East (or fly a MENA based airline) where as before you could choose from dozens of directs.