They have the joint biggest lead in top-flight history at this stage of the campaign and no team has ever failed to win the title with an advantage of this size.
Vernon Philander took four for 16 in 14.2 overs as South Africa appeared to have taken control by bowling out England for 181, a first innings lead of 103.
James Anderson marked his 150th test and return to the England attack with the first-ball wicket of home opener Dean Elgar, and Sam Curran also grabbed a scalp in his first over when Jonny Bairstow caught Aiden Markram for 20.
Harry Kane followed up his own shot to equalise in the 53rd minute and cancel out Adam Webster’s first-half header.
James Anderson marked his 150th cap and return to the England attack at Centurion Park with the first-ball wicket of home opener Dean Elgar, as Sam Curran and Stuart Broad took two scalps each.
The overhaul of South Africa’s coaching structure has given the team a major boost as they get ready to take on England in a four-Test series which begins on Thursday, captain Faf du Plessis said.
A statement from the England and Wales Cricket Board said that Ben Stokes' father, Ged, remained in intensive care in a Johannesburg hospital but had responded positively to treatment and was in a stable condition.
The 30-year-old Van der Dussen will bat at number five, captain Faf du Plessis said on Wednesday, in the place of Temba Bavuma who has been ruled out with a hip injury.
South African cricket has been in upheaval after a turbulent year during which the Proteas lost a home Test series against Sri Lanka before enduring a miserable Cricket World Cup in England and Wales and being trounced 3-0 in their World Test Championship debut in India.
Proteas cricket captain Faf du Plessis said he had never become a close follower of football but said meeting Jurgen Klopp had changed that.
