Rt 60 Springfield,MO to Paducah,KY

Right now they won't allow you over the Ohio River bridge due to bridge repair. Cops are at each end stopping people who ignored the warning signs. I was over that way recently. They have restrictions and one lane closed that eliminates all but passenger vehicles.

Do it.

But check to see if the bridge construction over the Ohio River at Cairo IL is finished..

I've done it twice in a C motorhome, many times in a car. Through Missouri, the road is great. Going into Cairo, through Cairo, and into Kentucky, depends on how you feel about roads that are just wide enough for large vehicles, filled with large vehicles, and minimal to no shoulder for emergencies. Not all like that, but there are sections that make some drivers uncomfortable.

You shouldn't have too much of a problem. Mostly hills and hollers, and Beautiful scenery. Road isn't all that bad, but remember you are choosing the shortest way..
If you haven't been to Paducah, plan on staying in the area for several days . A lot of history and a real neat town. We were only there for 1.5 days and did not see the whole area.
Oh yes and great RV parking right in town for visiting.:B Down by the museums.
Cheerrs
Chuck