I used to make underwater powerheads for shark protection. Now the only kill shot is a top down 12 guage on top of the head. A 12 guage to the body just makes them flinch.
I did a lot of snake hunting in the everglades, and I always stayed on the road with a double barrel. These were 6 ft water mocassins. Now as to a 300 pound python, I prefer my fat friend between me and that snake.