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The Bundesliga side's strength in depth proved the difference in Villach on Wednesday as former Real Madrid, Ajax and Milan striker Huntelaar showcased his predatory nous just before the hour.
Matip then added a second as Schalke followed up Sunday’s 1-1 draw with Besiktas with a morale-boosting victory.
Huntelaar was the most notable Schalke player introduced, Adam Lallana the pick of the Southampton substitutes sent on.
Lallana blazed over as Southampton pressed for an immediate response, but the result was put beyond any doubt when Matip doubled Schalke’s lead.
