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.
