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WASHINGTON (AP) — A high-stakes week got off to a bad start Monday for President Donald Trump, Senate Majority Leader Mitch McConnell and the GOP.

A key defection appeared to sink their health care drive anew, while another disappointment threatened Tuesday as the candidate backed by Trump and McConnell struggled in the polls in an Alabama Senate race runoff.

The twin blows, if both arrive, would leave Trump and McConnell looking for a win elsewhere. That arena could be taxes, where congressional Republicans and the administration will finally roll out their long-promised tax overhaul plan, “The largest tax cuts in the history of our country,” Trump promised Monday in an Alabama radio appearance on the “Rick & Bubba Show.”

Indeed, with failure now all but inevitable on the health bill, the tax push could stand by week’s end as the GOP’s last and only opportunity for a major political and policy win this year, a much-diminished outcome for an era of unified GOP control that began full of bold promises for achievement on many fronts. And success on taxes remains far from assured, with Wednesday’s roll-out serving as little more than a starting gun that will unleash ferocious lobbying over specific provisions in the code.

But on taxes, at least, failure does not yet loom as perhaps the likeliest outcome, as it does for Trump and McConnell’s other big gambles this week. The GOP health legislation now appears to have no path forward before a critical week’s end deadline, a reality acknowledged gloomily by senior Republicans late Monday. “It looks bleak at the moment,” said the No. 3 Senate Republican, John Thune of South Dakota.

And in Alabama, Trump and McConnell are both risking their political capital in support of the establishment candidate, incumbent GOP Sen. Luther Strange, who is in a tight race with firebrand former state chief justice Roy Moore, removed from the bench but beloved by evangelists in the state for his stands against gay marriage and for the public display of the Ten Commandments.

Moore is also strongly supported by some House conservatives and by former top Trump adviser Steve Bannon, who could claim a victory over his onetime boss, the president, if Moore wins the Senate seat previously held by now-Attorney General Jeff Sessions.

“It is very clear that Bannon has decided to make this a test of manhood vs. his old boss, Donald Trump,” said Steven Law, a former McConnell chief of staff who heads a super PAC that’s spending millions on behalf of Strange.

Moore supporters were projecting confidence. “I bet that Judge Roy Moore wins tomorrow night, overwhelming,” House Freedom Caucus Chairman Mark Meadows told reporters.

That outcome could also be dire for McConnell, diminishing his perceived political clout after a string of successes in contested primaries in recent years. And presuming Moore goes on to win the general election in December, he would likely become an unpredictable and uncontrollable force in a GOP conference that McConnell already struggles to corral.

The importance of a single vote in the Senate has been nowhere more evident than on health care, where the GOP was humiliated in July when its last repeal effort failed by one vote, in the dead of night, thanks to a decisive thumbs down from Sen. John McCain of Arizona. Trump railed against the veteran Arizona Republican Monday, calling his actions a “tremendous slap in the face.”

McCain is opposed to the current version, as well, even though it’s authored by his best friend Sen. Lindsey Graham of South Carolina as well as Bill Cassidy of Louisiana. Their bill, which would undo the central pillars of former President Barack Obama’s health law and replace them with block grants to states, is short of support ahead of a week’s-end deadline when it will lose special legislative protections from Democratic filibusters, thus requiring 60 votes to pass. Up until Sept. 30 it can pass with 50 votes, plus a tie-breaker from Vice President Mike Pence.

That makes this week’s maneuvering the GOP’s only avenue of success in face of unified Democratic opposition, but it remains a slim one in a Senate split 52-48 between Republicans and Democrats. Trump acknowledged as much Monday, all but predicting failure when he said, “We can’t lose any votes, practically, so we’re going to lose two or three votes, and that’s the end of that.”

Indeed Sen. Susan Collins of Maine confirmed her opposition late Monday, joining McCain and Sen. Rand Paul of Kentucky. That’s one more “no” vote than McConnell can afford to lose, and Sen. Ted Cruz of Texas also has said he’s opposed without changes. It was unclear whether McConnell would move ahead with a vote if he’s assured of losing.

“I doubt it,” replied senior GOP Sen. Orrin Hatch of Utah when asked whether McConnell would put the health bill on the floor this week.

Despite the busy and consequential week, Trump has chosen this time to pick a very public fight with the NFL over some players’ decision to take a knee during the playing of the national anthem. Press secretary Sarah Huckabee Sanders defended the president’s focus Monday, telling reporters, “It really doesn’t take that long to type out 140 characters. And this president is very capable of doing more than one thing at a time and more than one thing in a day.”