The biggest impact on this game will be Louisville's ability to stop Clemson's defensive line from getting penetration. Louisville has been able to do a great job running the football with the read option, traditional run plays, and inverted veer. They've also been able to do a great job giving Lamar Jackson the time to survey the field and find the open receiver.
The key to stopping a mobile quarterback is containment and the only way you can do that is if you have guys free to spy the quarterback. People think that speed is a big deal with spying quarterbacks but it's really about angles and free space for the defender.