49ers cornerback Richard Sherman was asked Sunday if the inability to tackle Cardinals quarterback Kyler Murray was the result of a worldwide pandemic nixing the NFL's 2020 preseason.

"Oh, no," he said after the reigning NFC champs fell in the NFL's biggest upset of the week. "No, no, no. That didn't change a thing. Preseason is the most unnecessary thing in the league."

No, Sherman said, the bigger problem was officials overprotecting Murray, an electric second-year player whose Week 1 performance just made Russell Wilson the second-most confoundingly elusive quarterback in the powerhouse NFC West.

So, Vikings fans, if you think you're disappointed heading into Week 2, you're not alone. People with even higher expectations share your pain.

Three of last year's six NFC playoff teams — 49ers, Vikings and Eagles — went 0-3 while being outscored by 23 points. They were favored by a combined 15 points.

Sorry, Minnesota. But San Fran, which started 8-0 a year ago, has you beat in level of Week 1 frustration.

The 49ers came out of the game with an injured George Kittle and only three healthy receivers. They're now alone in last place in the NFC West.

And they just got a surprising punch in the snout from what may be the Next Big Thing in their division and the conference — Murray, DeAndre Hopkins and a defense that might just be good enough for Arizona to make a playoff run a year after going 5-10-1.

In his Cardinals debut Sunday, Hopkins caught 14 passes for 151 yards. Murray threw for only 230 yards but ran the ball 13 times for 91 yards, including a 22-yard touchdown.

You also can add 30 more yards in penalties against the 49ers for ticky-tack late-hit penalties at the end of two Murray runs.

"The frustrating thing is when refs make the calls when he's running the football," Sherman said. "Guys are trying to go over him and halfway tackle him [to avoid the penalty].

"You don't know when to take the chance to tackle him or let him run. So that was the tough thing [Sunday]."

The most controversial of the two penalties was against Kerry Hyder at the end of an 8-yard run on second-and-22.

Murray was making a move when he suddenly slid headfirst. Hyder was committed to the tackle when he held up and went over the top of Murray.

"I don't love this one," Fox Sports rules guru Dean Blandino said on the broadcast. "It looks like the defender went over the top more. That seems like the type of contact the official should let go."

Sherman agrees.

"The penalty on Kerry Hyder, [Murray] is cutting back and making moves," Sherman said. "It's like once you commit to tackling a guy and he's in the middle of a move, you don't know if he's going to the ground or staying up. So I think that was the thing that made tackling more difficult."

Quarterbacks are running more, obviously. On Sunday, Cam Newton ran 15 times for 75 yards and two touchdowns; Josh Allen 14 times for 57 yards and a touchdown; rookie No. 1 overall pick Joe Burrow eight times including a nifty 23-yard touchdown; and even Kirk Cousins hit back-to-back gains of 16 and 14 yards.

"It's always harder with a running quarterback [to avoid unnecessary roughness penalties] because you don't know if he's going to slide or if he's going to continue to run," Vikings coach Mike Zimmer said "But we [teach defenders] to kind of assume that most quarterbacks are going to slide."

Murray isn't most quarterbacks. Last year's offensive rookie of the year might prove to be one of the greatest runners in the league.

On Sunday, he was facing third-and-7 in the third quarter when a teammate false-started. No problem. On third-and-12, he scrambled right, paused, juked some defenders and took off for 25 yards.

Four minutes later, he took off on first-and-10 from his 12.

Linebacker Dre Greenlaw closed in and was faced with two choices: Go for the tackle and risk being unable to stop his momentum if the jitterbug drops into a slide; or pull up and watch the jitterbug prance right by him.

Greenlaw chose the former. Murray dropped. Greenlaw tried to avoid contact but bumped Murray.

"There's not a lot of contact there," Blandino said. "But it is a foul by rule."

A rule that Murray and this enhanced offense will no doubt take full advantage of, as they did in knocking off the reigning NFC champs.

Mark Craig is an NFL and Vikings Insider. Twitter: @markcraigNFL. E-mail: mcraig@startribune.com