There's a huge difference being able to defeat/hurt a Royal Guard versus beating able to knock one down.
It is very possible to defeat one but you're not going to be able to knock one down because the physical strength required is something no human besides Uber Gon has. To put things into perspective, Pitou took a hit in the face from Meryem and also wasn't knocked down. Although Meryem may have underestimated Pitou's power, it's pretty safe to assume that even a casual hit from Meryem has far more physical power than any non Uber Gon human can possibly do. Even though Pitou was never expecting the attack, he still held his ground just fine. So an attack that can obviously can kill him if done enough times is still insufficient to knock him down even when he's not expecting it.
This means a strategy involving exchanging hits or even just doing physical attacks on Royal Guard is doomed to fail. No Royal Guard would even flinch from the trauma/impact of a physical attack delivered by a human. Again, this doesn't mean they're immune to it. The fights in HXH basically plays out like a fighting game, e.g. if A kicks B successfully then B cannot immediately counterattack because he got hit and is stuck in a recovery frame. However, that doesn't apply to the Ants. If you kick a Royal Guard, they can take damage, even significant damage, but they'll just hit you back at the same time they're taking damage because a human cannot exert enough physical force to put them in a recovery frame state. The only thing that can interrupt their attack would be something like a shocking attack which only Killua possesses. Since no human can possibly win in a straight up hit exchange it's a matter of time before you lose, because all a Royal Guard has to do let you hit them first and then immediately hit back the moment you make contact.
Now an appropriate strategy would likely involved ranged weapon and gadgets. Poison, as mentioned, would be a quite effective way to deal with them, especially given the Hunter possess quite possibly the strongest poison user in the world of HXH, Morel. Morel can conjure up clones of himself that can fool the Royal Guards for a short time (Yupi figured out where the real Morel is, but it sure wasn't immediate). He can create smoke that hides the existence of whatever poison he's using, and he is practically immune to any kind of poison gas since he can hold his breath forever. However having Morel throwing some gas grenades and taking out the Royal Guards wouldn't have made an interesting battle. Still, you can't just say 'the fights wouldn't have been fun' as an excuse. We're told that humans are willing to do whatever it takes to defeat the Ants, including detonating the equivalent of a nuke in the middle of a highly populated area (there is absolutely no evidence that Netero had a plan that can guaranteed Meryem would leave the palace), but apparently using stuff like poison gas is out of the question. Heck, if they borrowed the electric whip on the guy on the wheelchair from Celestial Arena, that could have actually turned the fight around.
By the way, the Potclean strategy pretty much requires Knuckles to be faster than Yupi. Let's look at how the foot speed of the characters in HXH match up. We know Pitou is faster than Netero (people seem to confuse his incredible hand speed with his foot speed), because Netero landed straight in the center of the palace while Pitou got knocked away a relatively large amount of distance. Further, Pitou was jumping up while Netero was jumping down when they encountered each other, which means Pitou must have landed quite a bit later after Netero landed (Pitou's En shows Netero is already inside heading toward Meryem while he was still in air). Both presumably found Meryem with En and took the shortest path possible to get there, and we know Pitou arrived at practically the same time as Netero Yet, Pitou has the lowest movement speed out of the Royal Guards, because Pitou cannot fly. Using the time Pufu used he had to try to kill Komugi prior to Meryem growing a pair of wings and after, we can assume that a winged individual is at least 5 times as fast as someone on foot (he estimated about 30 minutes prior to wings and around 5 minutes after). We see that Yupi can keep up with Pufu in air, so both should have relatively the same aerial speed.
Now even if Yupi somehow can't fly effectively in the middle of the battle, just comparing Pitou and Netero you'd get that Yupi should be able to catch up just fine unless either Yupi is much slower than the rest of the Royal Guards, or that Knuckles is much faster than Netero. I guess you can argue that Knuckles could've hide himself somewhere while still beating close enough to trigger Potclean, which would mean Yupi for some reason cannot do En greater than 100 meters (maximum distance for Potclean to trigger).
