Cristy - are you asking about something close to the Safari Park?
If so... that's a pretty empty stretch of interstate - as far as "chain" hotels goes. Roanoke is about 45 mins. South of the zoo and Lexington is about 13 miles to the North - there are a few chain hotels there. There is a hotel at Natural Bridge - it's not a chain - although I think it is popular because of the Natural Bridge attraction. (My parents have stayed there).
If you are traveling - summer/fall - Lexington also has a drive-in. We go there on a regular basis. You could do the safari zoo - then hit the drive in that night.
http://www.hullsdrivein.com/
P.S. - You might already know this - but I just found it recently and think it is Way Cool - to find a hotel (or restaurant, etc.) along a certain route such as Roanoke, VA to Lexington, VA - go to Google - then Maps - then Get Directions - then put in two locations - such as Roanoke, VA to Lexington, VA - and hit the "get directions" generator - - then at the top of the page in the search bar put in "hotels" - then hit Search Map. It will bring up flags for all of the hotels along the route. This has helped me on more than on occasion as we have traveled this summer!