So my plague is similar to a zombie virus, it's magical virus charged by negative energy that slowly drains a person to the point of death, then reanimates the corpse into a zombie. Dnd zombie not t.v. zombie. My idea was the plague was started by the cult of Orcus who desire to kill mass numbers of people, but I really don't know how something like this would be created. Does it make sense for Orcus a demon lord to gift them with such a plague, or would it make more sense for them to have created it? I was also basing the idea that to cure the plague the players have to get a magic relic to end it. Like a magic fountain. So what are your idea? How can I explain the creation of the virus?

It doesn’t need to be too deep. The players will be far more concerned with how to avoid contracting it and how to cure it than with how it came to be.  But sure, say Orcus created Patient 0 and sent him out to spread the disease. Alternatively, it’s just as/if not potentially more engaging to believe humanity brought the plague on itself through careless ambition.  It was meant to bring eternal health to the body, only they missed something and it drains its host to death before the regenerative properties kick in.  How it spreads is up to you, whether through contact, bites, whatever.

Seems like you do already know how it started, the Cult of Orcus did it. The exact mechanics, as kcb says, don't really matter. If I'm not mistaken, we never found out how things started on The Walking Dead, and they've certainly been able to milk the premise for a long time. In a case like you're describing, how it started, exactly, is less important than how people deal with it/end it.

But if you really, really want something, how about the Cult of Orcus developed a poison that would give the plague to whomever consumed it. They then sent a few dozen members (or however many serves the story/how widespread you want it to be) on suicide missions where they'd travel to a large city, maybe even multiple people to the same city. On a specified date, each member would drink the poison and then start walking around in public, crowded spaces, visiting inns, taverns, brothels, markets, anywhere people gather, with a particular focus on places like the docks, or caravan rest stops so they could be sure to infect people traveling to other locations. It could have a nice, long incubation period, so people will be walking around infecting others well before they realize they are sick.

As far as if it was the cult, or Orcus himself, either could work. The cult did it because one of the higher-ups wanted to impress Orcus, maybe try to earn a spot at his side. Orcus did it because he has deep plans that mortals can't possibly understand, and this was just one part.

A magic fountain might be tough in practice. How will they get the water from the fountain around to all the infected people in a timely fashion? Could be some two-part thing where they need to place some other artifact in the fountain and perform some kind of ritual in order to magically disperse the curative properties.

So maybe the fountain/magic item needs to be used in a location where the curing magic covers everywhere the plague has infected. Maybe it's a rod thats fueled by the water of the fountain, thus meaning it has one use. 

Maybe the rod works with water sources to create a fog cloud of healing mist (like a nebulizer for those of you with lung conditions that would know what that is.). The fog spreads to cover a whole village at a time. This cure could be brought from village to village, where applying the cure could be challenged in various ways. No central well or water source. High winds or other bad weather when ready to create fog. Monsters guarding water source. It’s gone dry. Honestly, might be a good situational use for the create water spell.

You could take kcb's idea and have it work with any water source. Or maybe make it have to be holy water. If you have a cleric who can create it, great, if not, they need to find one locally to help them. Maybe the cure works like the plague did -- be cause some god or another wanted to be able to counter Orcus. People exposed to the cure become immune to the plague, and they are able to spread that immunity in the same way the plague spread, like an anti-plague.

The PC's would still want to travel around and start the process in multiple places to try and hit a critical mass of anti-plague vs. plague. Just don't make them do it too many times, cause it could get boring just going from town to town sticking a rod into some water. Maybe three - four times. After that there's enough immune people walking around that things will sort themselves out, generally.

Then the campaign could continue with the aftermath. Lots of people have died, political situation is destabilized, trade has slowed since people don't trust people from other towns. There's still some nests of plague zombies floating around to stamp out, etc.

With that in mind the players main focus could be the biggest city in the area, which means hey have to take care of the city then smaller settlements that weren't so luckly