The Seven Deadly Sins could also be the main antagonists. Their evil nature doesn't depend on Billy's gender. However, as a female, Billy might have a different approach to fighting them. Maybe they'll try to use her newfound vulnerability (as she adjusts to her new form) to their advantage.
Dr. Sivana could still be the main antagonist. His hatred for Shazam wouldn't change just because Billy is now female. In fact, he might be even more enraged or intrigued by this new development and try to take advantage of it in some way.
One possible plot could be that as a female, Billy (let's call her Billie now) discovers new aspects of the Shazam powers. Maybe she has a different approach to using the powers for good in Fawcett City. She might face unique challenges from the villains who are not used to a female Shazam. For example, they might underestimate her at first, but she quickly proves them wrong with her newfound strength and the wisdom of Solomon which she uses in a more empathetic way as a female.
A new villain could be the kidnapper. Maybe a powerful interdimensional being who has heard of Shazam's powers and wants to study Billy to find a way to bring those powers to his own dimension. This being would be extremely powerful and Billy would have to find a way to outsmart him using his own wits and the powers of Shazam.
One idea could be that as Billy turns into a female, she has to deal with different social expectations in Fawcett City. For example, she might find that people treat her differently when she's out as Shazam in her new form.
Maybe a corrupt Shinigami officer who has always been against Ichigo. When he hears about Ichigo's transformation into a female Arrancar, he uses it as an excuse to label her as a dangerous outcast and tries to hunt her down. This officer could be power - hungry and see Ichigo as a threat to his own rise in the Soul Society.
A jealous male trainer could be the main antagonist. He might see Ash's transformation as an unfair advantage given by some mysterious power. He constantly tries to undermine her in battles and challenges, believing that a female should not be as successful as a male in the Pokemon world.
A powerful and corrupt Pokemon trainer could be the antagonist. This trainer is jealous of the boy's unique transformation into a Pokemon. He wants to use the boy's powers for his own gain, like winning all the Pokemon battles and championships. So, he hunts the boy down, causing all sorts of trouble for him during his journey as a Pokemon.
Maybe Team Rocket could be the main antagonist. They might see Ash's transformation as an opportunity to finally capture Pikachu. Since Ash is in a more vulnerable state as a girl, they could try to use different tactics to take advantage of the situation.
Perhaps a jealous trainer. This trainer has always been envious of Ash's success and now that Ash is in a vulnerable state as a Zorua, the trainer sees an opportunity to get rid of him for good. The trainer could try to use his own Pokémon to capture Ash or even harm him, making the trainer a formidable antagonist in the story.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.
Maybe a powerful and envious Mewtwo could be the antagonist. Since Ash has now become a Mew, Mewtwo might feel threatened or think that Ash doesn't deserve such power. So, Mewtwo could try to fight Ash to prove his own superiority.