Assuming that the Antonov 225 cannot
achieve sustained level-flight speeds of 500mph near sealevel [due to air resistance at SL] which would be a perfectly good assumption...It probably could not achieve 500mph below 30,000ft.
Then...48 jumbo jet-engines for 500,000 tons of flying hardware may not be enough, even cruising at 100mph a little above SL.
Since air-density at 30,000ft is roughly 1/3rd that of air-density
near SL, then what may be needed are 48 jet-engines/0.33 = 144 engines...

Still a long way from
6000 jet-engines.

144 jet-engines. 36 per pair of wings [or mounted in rows on the fuselage] still seems doable.
What's more!...The fuselage/wing problem [500,000 tons is alot of stress
to put on the wings and fuselage] can partly be solved by using carbon-fiber/kevlar composites instead of aluminum-alloys [WHERE POSSIBLE] and partly by designing the fuselage to
give it airfoil properties of lift as much as possible.

Somebody is going to ask: "Where did I get the figure of 200,000 people crammed into such an hypothetically monstrous aircraft?
The answer is...The ship, the QUEEN MARY, 50,000tons displacement, crammed 20,000 GI's returning home to America after WW2. So it stands to reason that a 500,000ton craft can cram 200,000 people.

Jacob