The Mali international continued from where he stopped in the last matchday against the same opposition after he laid on an early opener for Hector Herrera to put the hosts in front two minutes after kick off.
In the 42nd minute, Marega doubled his side's lead off an assist from the Mexico midfielder.
Jefferson Farfan pulled one back for the Russians but Jesus Corona's strike and a late Otavio effort wrapped up a comfortable victory for the Portuguese champions.
Marega has now scored three goals in the competition to help Porto stay at the top of Group D with ten points.
On the other hand, Lokomotiv have been dumped out of the European elite club tournament after losing all their opening four games.