Alot of that decision would depend on what your opponent has been doing up to that point.
You say he is running a out and sending the other 2 WR's deep or one deep and one short ?
Assuming he is running an out with the 1 WR on the weak side call a 3 Weak. Your CB on the weak side is playing the zone he would play if he were in cover 2 soft. You can even hot route him to play man to insure he follows that WR wherever he goes and shade him outside. The 2 safetys are in zones that take away the corner route and the post route if the other 2 WR's are running those routes. You can also hot route the DB/LB on that side to man coverage on one of the other WR's of your choosing of the remaining 2 WR's or go one further depending on tendency and faith in your MLB and have him man up on the 3rd WR.
Thas if you want to play 3 deep. You could call 4 deep and man up one of the under guys on the 1 WR. You could also go dime 2 deep with man under coverage.
You could also just call a 3 LB Blitz and hurry him into trying to throw that out to fast and get a INT. With 3 wides on one side he only gonna have at the most 1 back in to help pick up the blitz and he aint gonna have time to throw a corner or post.
Again, I aint no guru, I just go off basic knowledge and adapt to what I see happening the best I can. You win some you lose some. If the guy can make the reads fast enough and has players that can beat your players he is gonna win some of the downs. Thats just football. You gotta do whatever you can to confuse and make your opponent do things he does not want to do and hurry him into mistakes. If he developes a pattern to where he likes to throw the ball then take that zone away from him and make him beat you somewhere else.
People complain about people who only throw outs but they will be the easiest people to beat because alot of the time thats all they got offensively. Once you take that from them they either keep forcing the ball there and getting picked, or try and find another route they see that you have not figured out how to stop, or they give up and quit which is what we all see alot of online.