The short answer is yes. The long answer is that the Supreme Court would have to get involved. And they are very reluctant to make any kind of new interpretation of the Constitution for something like this.
Any answer to the question would be a new interpretation, since the clause hasn’t previously been litigated.
But you can clearly amend the powers of the Senate, including abolishing all of them. And/or create a third house of Congress, without equal per-state representation.
I wouldn’t be so sure; it would require getting states to vote against their narrow parochial interests, but it's not inconceivable that it could happen. It would probably take a crisis of legitimacy in which the disaffection of the underrepresented states was sufficient to threaten the viability of the union, though.
I've imagined a workaround where states would be de-stated if they fell below a threshold percentage of the total population or be required to split if they grew above an upper bound percentage. The only reason there are two Dakotas is to give the Republicans two extra senate seats (this is true, you can look it up).
> The only reason there are two Dakotas is to give the Republicans two extra senate seats
First of all, you have no idea what you're talking about. The two Dakota territories gained statehood in 1889, long before there was any kind of notion of the modern-day Republican party.