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President Donald Trump said the United States would not kill Iran's supreme leader "for now" and appeared to demand Tehran's surrender, as US ally Israel traded fire with its arch foe for a fifth day on Tuesday.
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The comments marked a dramatic escalation in Trump's rhetoric against Iran and its leader Ayatollah Ali Khamenei, fuelling questions as to whether Washington would join Israel's attacks after insisting it had no hand in the campaign.
Israeli warplanes targeted drone and missile sites with at least two waves of strikes in western Iran on Tuesday, the military said.
It also said it had killed senior Iranian commander Ali Shadmani in an overnight strike on a "command centre in the heart of Tehran", just four days after his predecessor, Gholam Ali Rashid, was killed in Israel's initial surprise attack.
The attacks drew retaliatory fire from the Islamic republic, with explosions heard over Tel Aviv and Jerusalem, and air raid sirens sounding around Dimona, a southern town home to a nuclear power plant. There were no immediate reports of hits.
Days after a senior US official said Trump had told Israel to back down from plans to assassinate Khamenei, the US president appeared to put the option back on the table with a post on his Truth Social platform.
"We know exactly where the so-called 'Supreme Leader' is hiding. He is an easy target, but is safe there -- We are not going to take him out (kill!), at least not for now," Trump said.
"But we don't want missiles shot at civilians, or American soldiers. Our patience is wearing thin," he added, later posting a message saying: "UNCONDITIONAL SURRENDER!"
Trump had said earlier in the day that he wanted "a real end" to the conflict.
A White House official said Trump was convening a meeting of his National Security Council Tuesday to discuss the conflict.
Despite mounting calls to de-escalate, neither side has backed off from the aerial blitz that began Friday, when Israel launched an unprecedented bombing campaign targeting Iranian nuclear and military facilities.
- 'Punitive operations' -
Iranian media reported several explosions Tuesday in the central city of Isfahan, home to nuclear facilities. Blasts were also heard across Tehran.
The Iranian armed forces warned residents in the Israeli cities of Tel Aviv and Haifa to evacuate "for the sake of their lives", warning of "punitive operations" to come.
Iran's Revolutionary Guards said they had launched an attack targeting Israeli air bases.
Residential areas in both countries have suffered deadly strikes since the fighting broke out, and foreign governments have scrambled to evacuate their citizens.
A cyberattack on Tuesday crippled Sepah Bank, one of Iran's main state-owned banks, the Fars news agency reported.
Fearing the violence, many residents have fled Tehran.
On Tuesday, long queues stretched outside bakeries and petrol stations as the remaining residents rushed to stock up on fuel and basic supplies.
Security checkpoints have been set up across the capital, adding to the atmosphere of tension as authorities monitor movement in and out of key districts.
Pentagon chief Pete Hegseth said the United States was deploying "additional capabilities" to the Middle East, with a US aircraft carrier reportedly heading to the region.
Even before Trump's remarks about Khamenei, China had accused him of "pouring oil" on the conflict.
Turkish President Recep Tayyip Erdogan accused Israeli leader Benjamin Netanyahu of being "the biggest threat to the security of the region".
At a G7 summit in Canada, leaders including Trump had called Monday for "de-escalation", while stressing Israel had the right to defend itself and that "Iran can never have a nuclear weapon".
- 'Direct impacts' -
After decades of enmity and a prolonged shadow war, Israel said its surprise air campaign aimed to prevent Iran from acquiring nuclear weapons -- an ambition Tehran denies.
The UN's nuclear watchdog said there appeared to have been "direct impacts on the underground enrichment halls" at Iran's Natanz facility.
The conflict derailed a running series of nuclear talks between Tehran and Washington in recent weeks, with Iran saying after the start of Israel's campaign that it would not negotiate with the United States while under attack.
Since Friday, at least 24 people have been killed in Israel and hundreds wounded, according to Prime Minister Netanyahu's office.
Iran said on Sunday that Israeli strikes had killed at least 224 people, including military commanders, nuclear scientists and civilians. It has not issued an updated toll since then.
Netanyahu said Israel's campaign was "changing the face of the Middle East, and that can lead to radical changes inside Iran itself".