Hopgood was injured in the first half of the Eels' 30-20 win at CommBank Stadium on Sunday, after Dragons forward Ryan Couchman fell on the back of his legs in a tackle.
The 26-year-old limped from the ground and Couchman was sin-binned, but Eels medical staff have already determined that the former Queensland State of Origin forward's season is over.
"It's really disappointing ... that's his season," Ryles said.
"Those tackles, 99.99999 per cent of the time the boys don't mean it. So it's not intentional.
"But unfortunately you keep throwing fatigue into the game and you keep making them tireder and tireder and tireder and tireder, they happen.
"So that's the reality. You've just got to practise and mitigate it as much as you can and hope that it doesn't happen."
In a further blow for Parramatta, centre Jordan Samrani is also set for scans on his knee after limping off in the first half. He is not believed to have suffered ACL damage.
Set-restart calls increased by 78 per cent in the NRL over the opening two rounds compared to last year.
That has come with ruck-infringements and offsides now triggering set-restarts rather than stoppages for penalties between the 20 and 40-metre line, when teams come out of their own end.
Hopgood's devastating injury soured an otherwise fine day for Parramatta, with Tallyn Da Silva having his best game in Eels colours.
The hooker scored two tries and played a key role in another, as his side came from 14-4 down to win.
Thrashed by Melbourne in round one and down 20-6 early against Brisbane last week before winning 40-32, Parramatta are now 2-1 after three rounds.
The Dragons, meanwhile, are winless after three games for the first time since 2020 despite being in each of those contests until late.
The difference on Sunday was what both teams were able to do with a one-man advantage.
With Parramatta trailing by 10 late in the first half, Mitch Moses and Da Silva proved vital while Couchman was in the sin bin.
Moses first made his impact when he ran the ball on the last tackle, catching the Dragons on the back foot and giving Jonah Pezet the space to send Da Silva in to score.
Moments later, Da Silva went to dummy-half for a quick Matt Doorey play-the-ball and sent second-rower Kitione Kautoga over to make it 18-14.
The Eels hooker then scored a try of his own after the break when he feigned to the right and darted over from close range at dummy-half.
After arriving as a high-profile mid-season signing from Wests Tigers last year Da Silva has spent most of his time coming off the bench, but this was his best outing so far.
In comparison, the Dragons couldn't nail the key moments when Parramatta's Charlie Guymer was sin-binned for a professional foul in the second half.
They scored once through a Moses Suli grubber for Kyle Flanagan, but otherwise failed to make the most of space to the left on multiple attacking raids.
The Red V's fate was sealed with Guymer back on the field, when Valentine Holmes spilled a pass and Josh Addo-Carr went 70 metres to score.
"We just beat ourselves to be really honest," Dragons coach Shane Flanagan said.
"Every stat, we were in front. But we couldn't win on the scoreboard and that's all that matters."
