I have not seen any mention of VA-42 upthread, which is chopped up into three segments.
Not so far away, the Blue Ridge Parkway can be closed during the winter season for the usual reasons in both Virginia and North Carolina. Otherwise, it's just long
Then there's the matter of Quebec Route 138 (I have been on a few parts of this long ago).
From the U.S. border to Kegashka is long but possible, then there are several isolated segments that are not connected to other roads (one at La Romaine, maybe another at Chevery, another at Tête-à-la-Baleine, and maybe at La Tabatière). These appear to be reachable by coastal ferry.
The section from Old Fort (Vieux Fort), Quebec and east connects to the North American road network across Labrador.