Study your geology Smaug, half a billion years ago, the world was transgressing from the Cambrian to the Ordovician age, while the Panama Isthmus was formed only just after the beginning of the Pliocene.
Well, so would the sentient bird evolution TL (
https://www.alternatehistory.com/discussion/showthread.php?t=35036)
and the dinosaurs survive in the America's TL (
https://www.alternatehistory.com/discussion/showthread.php?t=48975)
Especially in the latter one, the evolutionairy butterflies would be major,
and far greater than those of a small Panama Strait instead of Isthmus.
I agree with Tom Veil that EmptyOne's suggested scenario is the easier
one to work with, hence a small strait with very little Atlantic-Pacific sea currents
would make the smallest difference when compared to the OTL situation.
I would also say that the lionshare of the Marsupial and Xenarthra fauna would survive, and even with a possebility that marsupial hyena's, opossums the size of coyote's and even sabretooth marsupials would survive at least well into the human age of that TL (provided there are no notable differences in global climate with OTL, so human evolution and development are not notably interrupted or changed).
But I doubt wether it was just the Native Americans who wiped out the megafauna by overhunting species.
Personally, I think it was rather a combination of the factors of (over)hunting by humans and the stress of a climate change (the ice age), and then there is a quite plausible third theory that I've heard about: the introduction of certain new animal diseases that tend to jump species that put an end to much of the native megafauna, which was already weakened by climate change and being hunted by humans.
There are existing animal diseases with high mortality rates that have been known to jump species successully, such as rinderpest and canine distemper.
The theory is that this disease was not spreaded by the humans directly, but mostly via the dogs that came along with the humans, as well as their flees.