Sistani said in a statement Thursday that any targeting of Iran's "supreme religious and political leadership" would have "dire consequences on the region".

He warned that such action against the Shiite-led Islamic republic could spark "widespread chaos that would exacerbate the suffering of its (the region's) people and severely harm everyone's interests".

Sistani urged the international community to "make every effort to end this unjust war and find a peaceful solution" to concerns about Iran's nuclear programme.

Sistani, an Iranian, is the highest religious authority for millions of Shiite Muslims in Iraq and around the world, with the power to mobilise a huge following in Iraq.

Despite his Iranian roots, Sistani is seen as a key figure in Iraq's recent history and has been known for pushing back against Tehran's growing clout in the country.

Israel's Defence Minister Israel Katz said Thursday that Iran's supreme leader Ayatollah Ali Khamenei "can no longer be allowed to exist" after an Israeli hospital was hit during an Iranian missile attack.

Earlier this week, Israeli Prime Minister Benjamin Netanyahu did not rule out plans to assassinate Khamenei.

US President Donald Trump had earlier said his country would not kill Khamenei "for now", but demanded Tehran's "unconditional surrender" and warned he was weighing military action in the conflict.

Israel launched a surprise attack Friday targeting Iran's military and nuclear sites and killing top commanders and scientists, saying it is acting to prevent Iran from obtaining a nuclear weapon, an ambition Tehran denies.

The assault has prompted Iran to retaliate with barrages of missiles on Israel, with residential areas in both countries suffering too.

Iraq's National Security Adviser Qassem al-Araji urged the European Union on Thursday to exert pressure on Israel to stop the war, ahead of a meeting between Iran and European powers.

With warnings of all-out regional war intensifying, fears are growing over an intervention by Iran-backed Iraqi factions, mostly against American interests in the region.

- 'Destruction' -

Akram al-Kaabi, the leader of the pro-Iran group, Al-Nujaba, warned the United States against going after Khamenei.

"If you harm a hair" of Khamenei's head "you and your allies will be under our fire," Kaabi said in a statement.

"No soldier or diplomat will be spared," Kaabi said.

"Every person holding your nationality in our region, as well as all your direct or indirect interest will be a legitimate target," he added.

The powerful faction Kataeb Hezbollah said that Trump "made a mistake" when he spoke of Khamenei and warned the US president of "unprecedented calamities and destruction" if he goes into war in support of Israel.

In Lebanon, Iran-backed militant group Hezbollah warned against threatening Khamenei, describing it as "an act of recklessness and foolishness" that would have "grave consequences".

It "constitutes an offence to hundreds of millions of believers", added the group, which suffered heavy blows in its latest confrontation with Israel last year.