The Serum Supernus is the 'ultimate potion' and brewing it is the ultimate goal of Plague Knight and Mona in the Plague of Shadows Campaign. To complete the potion Plague Knight must attain the essence of The Enchantress, the other members of the Order of No Quarter and Shovel Knight.

When he successfully combines all essences the Serum Supernus transforms into the Plague of Shadows and then the Corrupted Essence. When both have been defeated it stabilizes and turns back into a potion. Plague Knight, having decided he no longer needs it, uses it to level the Tower of Fate.

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