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Despite the nuclear destruction of Raccoon City, the T-Virus has escaped containment. Unable to be contained by the Umbrella Corporation, the virus quickly spreads across the world, drying up the lakes, rivers, and continents while infecting the human population and spreading to other species. Five years later, The Umbrella Corporation appears to be the only human authority left, its remnants forced to live underground in Hive-like constructs around the world.
Alice (Milla Jovovich), is now alone in the desert wastelands of the remains of the United States. She has superhuman strength and psionic abilities gained from Umbrella. Dr. Sam Isaacs (Iain Glen) considers re-capturing Alice a top priority because of her ability to bond with the T-Virus and attempts to persuade the rest of the Umbrella board that he can use her blood to develop a permanent cure, as well as tame the infected. Umbrella chairman Albert Wesker (Jason O'Mara) orders Isaacs to create a cure using clones of Alice created from the blood of the original and refuses to authorize manpower to recover Alice until they are 100% sure of her location.