re: Inevitable?
Yes it was. "Staying home" as you put it wasn't going to be the status quo forever. The people living in the Western hemisphere were going to eventually make contact with the rest of the world and when they did their fate was sealed. They had virtually no immunity to the diseases of the Old World, and it was only a matter of time before they came into contact with them. The population of what is now the Eastern United States was already decimated by the time Jamestown was founded. Disease, not guns, is what wiped them out. This would've been the case regardless of who found who first.