Tests performed at the US Centres for Disease Control and Prevention identified the new strain that has yet to be named, said Barry Schoub, executive director of the National Insititute of Communicable Diseases (NICD).
"The virus is new in terms of its genetic make up and there is currently no vaccine against it," Schoub told reporters, adding that it had "high lethal potential for humans."
According to the department of health, the disease was first identified in a woman airlifted from Zambia to a Johannesburg hospital in September.
The woman later died. A member of the medical staff who accompanied her, a nurse and a hospital cleaner who came into contact with them, also died.
"A last person who is currently under observation at a hospital is responding well to (anti-viral) treatment," said Janusz Paweska, head of a special pathogens unit at NICD.
He said about 100 more people were still being monitored for possible symptoms of the virus, but they appeared to be out of danger.
The virus has previously been linked to the Lassa fever virus of West Africa.
No cases of the virus had been reported in Zambia where the disease is beleived to have originated.