Castel Gandolfo, Italy - Pope Leo said Tuesday threats to civilian targets in Iran were "unacceptable", speaking after President Donald Trump said a "whole civilization will die" if Tehran defies his latest ultimatum.

"Today... there was this threat against all the people of Iran, and this is truly unacceptable," the pope told journalists, without mentioning the US, which is at war with Iran.

He spoke as he left his residence in Castel Gandolfo, outside Rome, for the Vatican.

"There are certainly questions of international law, but much more than that, it is a moral question," he said.

His comments came just hours ahead of Trump's 8 PM ET deadline.

The US president warned Tuesday "a whole civilization will die" if Iran does not open the Strait of Hormuz by then.

Iran has closed the Strait – a key transit route for Middle Eastern oil – for weeks, since shortly after the US and Israel launched attacks on February 28, igniting a global energy shock.

Leo, the Catholic Church's first US pope, said "attacks on civilian infrastructure is against international law".

He urged those involved in the Iran war to "come back to the table".

"Let's talk. Let's look for solutions in a peaceful way," he said.

The pontiff also urged "the citizens of all the countries involved to contact the authorities, political leaders, congressmen, to ask them, tell them to work for peace and to reject war always."