Kohli will want to banish the memories of a poor New Zealand tour and lead the show.
He will get immense support from Shreyas Iyer and KL Rahul at number four and five.
India also have options in the middle with Manish Pandey and the versatile Shubman Gill available.
Meanwhile, Rishabh Pant is the second-choice keeper.
India's 15-member squad to face SA
A look at the Indian squad to face South Africa: Shikhar Dhawan, Prithvi Shaw, Virat Kohli (captain), KL Rahul, Manish Pandey, Shreyas Iyer, Rishabh Pant, Hardik Pandya, Ravindra Jadeja, Bhuvneshwar Kumar, Yuzvendra Chahal, Jasprit Bumrah, Navdeep Saini, Kuldeep Yadav, Shubman Gill.
A look at the options in bowling
With Pandya and Ravindra Jadeja as all-rounders in the side, India could be fielding both of them at number six and seven respectively.
India could then go with four specialist bowlers.
Jasprit Bumrah leads the pace-bowling show. He is supported by Navdeep Saini and Bhuvneshwar Kumar.
Wrist-spinners Kuldeep Yadav and Yuzvendra Chahal come in as prime options.
SA will hope to catch India off guard
Meanwhile, South Africa announced their squad for the series against India.
After a disastrous ICC World Cup 2019, SA saw the series against England ending in a 1-1 draw.
They beat Australia 3-0 in the recently-concluded ODI series.
SA will be aiming to continue with this momentum and catch India off guard.
India were thrashed 3-0 by NZ in ODIs.
Here's the squad of SA against India
Here's the SA squad: Quinton de Kock (captain and keeper), Temba Bavuma, Rassie van der Dussen, Faf du Plessis, Kyle Verreynne, Heinrich Klaasen, David Miller, Jon-Jon Smuts, Andile Phehlukwayo, Lungi Ngidi, Lutho Sipamla, Beuran Hendricks, Anrich Nortje, George Linde, Keshav Maharaj.