The 10-year-old would have been trying for a fourth successive win in next Friday's blue riband, but he broke a blood vessel on the gallops yesterday. "It is sad news. I had a call from Henrietta (Knight). You know what happened on the gallops - he bled through the nose," Lewis revealed.
"It's very sad and very disappointing for all of us. I have had people coming in here crying their eyes out.
"You would think it was a disaster. Well, it isn't a disaster, a tsunami is a disaster.
"I'm really sorry for everybody that lost money, including myself, but we are hopeful that he will be back to normal next year. Whoever wins the Gold Cup this year, I shall wish him all the best and remind him that he has only borrowed it."
Miss Knight had been putting the finishing touches to Best Mate's preparation in a piece of work on fellow trainer Mick Channon's gallops.
Lewis explained: "He went on the gallops at about 9.30am and Jackie (Jenner, Best Mate's groom) was not happy with him as he got into the middle of his work. She slowed him down because she wasn't happy with him and pulled him to a halt, and there was blood coming down the nose.
"The vet has seen him and he said there's absolutely no way he would run, so the dream has come to a temporary end."
Robert Alner, who trains new Gold Cup favourite Kingscliff, believes some of the shine has been taken off the race. "I'm absolutely gutted for them," he said. "I can imagine how disappointed they are. It is such a shame - you almost feel like it is one of your own horses.
"Best Mate is a true champion and now he can't come back to defend his crown. Whoever wins this year will always feel that they won because Best Mate wasn't there.
"Unfortunately these things happen in racing and you just have to get on with it, but I'm just gutted for them as they are such nice people and he is such a good horse."
Kingscliff's big-race jockey Andrew Thornton echoed those sentiments, adding: "It's one of those things. The race is going to be poorer for it."
Paul Nicholls is responsible for Gold Cup second favourite Strong Flow, a horse who suffered a possible career-ending injury in 2003.
Nicholls believes he can particularly relate to how the Best Mate team are feeling at present, given that his leading John Smith's Grand National hope Silver Birch was ruled out of the Aintree race just last week.
"It shows what we are all up against at the moment when you've got all these nice horses getting ready for Cheltenham. Anything can happen and one feels for Hen and Terry (Biddlecombe) - they will be gutted," he said. "That's what happened to us with Silver Birch last week. These things do happen and we have to learn to live with it."
Trainer Philip Hobbs, who could send Farmer Jack for the Cheltenham showpiece, added: "It's very disappointing for the connections and a shame the horse has been denied a chance to win a fourth Gold Cup."
Best Mate is now set for a long summer break and Miss Knight is hoping he can bounce back in style next season.
"Whenever they break a blood vessel it is serious, but it is not career-threatening and hopefully he will come back as good as new next season," she said. "But it will not have healed in time for the Gold Cup, so it is very disappointing."
Best Mate was the general 5-2 favourite for the race despite being well beaten by Beef Or Salmon on his last start at Leopardstown over Christmas.
He was found to be coughing after that race, and Miss Knight feels the virus that laid him low may be responsible for the current problem.
She said: "These things are often caused by a virus and he had picked one up while he was in Ireland, and I think it is all linked. He will have a long rest now, though, and will not run again this season."
Intended big-race jockey Jim Culloty, who was in action at Wincanton yesterday, did not comment.