Iran's Supreme Leader Ayatollah Ali Khamenei has said European nations including the UK "cannot be trusted" but Tehran is not against negotiating with anyone - except the US.
Delivering his first sermon in eight years in Tehran, the top cleric branded Donald Trump a "clown" who only pretended to support the Iranian people and would "push a poisonous dagger" into their back.
Mr Khamenei also hailed missile strikes against US targets in retaliation for the assassination of Iran's top military commander as a "slap on the face" to the superpower.
American forces have now revealed that 11 troops were injured in the attack, after initially saying no service personnel had been hurt.
In response to Mr Khamenei's comments, President Trump said in a tweet that the "so-called 'Supreme Leader' of Iran" should "be very careful with his words!"
Mr Khamenei's defiant address came as the Iranian leadership faced pressure both at home and abroad.
Thousands had gathered inside the grand mosque in central Tehran and packed the surrounding streets, chanting "Death to America".
Iran has been rocked by protests after the military admitted to mistakenly shooting down a passenger plane , killing all 176 passengers on board, in the tense hours after the missile attack.
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The regime had initially covered up its role in the downing of the airliner, leading to angry public demonstrations, brutally suppressed by security forces.
Mr Khamenei described the crash as a tragedy and a very sad incident that was used by Iran's "enemies", used to overshadow the killing of Major General Qassem Soleimani , whose funeral drew huge crowds onto the streets .
The deadly drone strike against the military leader showed Washington's "terrorist nature", he said.
Referring to Tehran's show of force in response, Mr Khamenei added: "The fact that Iran has the power to give such a slap to a world power shows the hand of God."
Tensions between Iran and the US have steadily ramped up since Mr Trump withdrew from Iran's 2015 nuclear deal with world powers, which imposed curbs on its nuclear programme in exchange for the lifting of international sanctions.
The White House has subsequently slapped crippling sanctions on Iran, including its vital oil and gas industry, pushing the country into an economic crisis that has triggered unrest.
Mr Trump has openly encouraged the protesters - even tweeting in Farsi - in a bid to destabilise America's longtime foe.
After Maj Gen Soleimani was killed in Baghdad, Iran announced it would no longer be bound by the limitations in the nuclear agreement.
Britain, France and Germany, who have been trying to salvage the unravelling deal, responded by triggering a formal dispute mechanism that is aimed at bringing Iran back into line and could result in further sanctions.
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Mr Khamenei, who was always sceptical of the nuclear accord, told worshippers the European countries "cannot be trusted" and said they were too weak to "bring Iranians to their knees".
He said they were "contemptible" governments and "servants" of the US.
However, he added that Iran was willing to negotiate, but not with Washington.
The 80-year-old has held the country's top office since 1989 and has the final say on all major decisions.
He last delivered a Friday sermon in 2012, when he called Israel a "cancerous tumour" and vowed to support anyone confronting it.
He also warned against any US strikes on Iran over its nuclear programme, saying the US would be damaged "10 times over".
Meanwhile, Russian Foreign Minister Sergei Lavrov has said Iran's accidental shooting down of the Ukrainian jet happened at a time when Tehran was rattled by reports of advanced US stealth fighters in the area.
He said: "There were at least six F-35 fighters in the air in the Iranian border area (at the time).
"This information has yet to be verified, but I'd like to underline the edginess that always accompanies such situations."