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When a lethal virus is believed to have taken over a passenger plane, Captain James Holland (Richard Dean Anderson) frantically seeks an emergency landing in a safe haven. According to specialists on the ground, no doctor can cure them, and if the virus is what they think it is, it has the power to kill millions within days. Now, as no country will receive them, and the CIA wants to shoot them down, it's up to Holland to navigate a maze of attacks, prove to the government that the 256 innocent passengers are not infected and save the lives of everyone on board.