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Other organisations include financial services group Sanlam and African Rainbow Minerals (ARM).
The Motsepe pledge comes after South Africa's president Cyril Ramaphosa recently said the Rupert and Oppenheimer families had each contributed R1 billion to assist with the coronavirus cause.
Motsepe Foundation founder and chairman, billionaire Dr Patrice Motsepe, said several hundred million rands would be immediately made available to help with saving lives and slowing the spread of the virus.
The foundation would also provide water to poor rural and urban communities to enable regular hand-washing and improved sanitation, among other measures.
Motsepe chairs Harmony Gold, founded and chairs ARM and is deputy chairman of Sanlam.
His wife, Dr Precious Moloi-Motsepe, has also announced a R5 million donation by the Motsepe Foundation to help the University of Cape Town manage its multi-faceted response to the pandemic.
Moloi-Motsepe was appointed UCT chancellor on January 1.
South Africa started a 21-day nationwide lockdown on March 26 to stem the spread of the virus in the economically fragile country, which received a junk credit rating from Moody's this month.
Harmony, which has nine underground mines and an openpit operation in South Africa, plus assets in Papua New Guinea, has said it was in full support of the lockdown and was putting its South African mines on care and maintenance.