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Russia has warned that any attempt to assassinate Iranian Supreme Leader Ayatollah Ali Khamenei would "open Pandora's box" and spark a dangerous escalation across the region, in its strongest remarks yet on the Israel-Iran conflict. 

Kremlin spokesman Dmitry Peskov told Sky News at the Constantine Palace in Saint Petersburg on Friday that regime change in Iran is "unacceptable," warning that such a move would incite "extremist moods" in the country.

"Those who are speaking about (killing Khamenei), they should keep it in mind. They will open Pandora’s box,” Peskov warned. 

His comments came after US President Donald Trump said he would decide whether to join Israel's military campaign against Tehran within two weeks.

Trump had earlier speculated online about assassinating the Iranian leader.

“The situation is extremely tense and is dangerous not only for the region but globally,” Peskov said. “An enlargement of the composition of the participants of the conflict is potentially even more dangerous. It will lead only to another circle of confrontation and escalation of tension in the region.”

Moscow has grown increasingly concerned about the trajectory of the conflict as it fears losing a key Middle Eastern partner.

Iran and Russia signed a strategic partnership agreement in January, deepening cooperation since the war in Ukraine began.

When asked if Russia would retaliate if Khamenei were killed, Peskov said such a development would have internal consequences in Iran. "It would lead to the birth of extremist moods inside Iran," he noted.

While Trump said he rejected President Vladimir Putin’s mediation offer, reportedly telling him to “mediate your own conflict,” Peskov downplayed the remark.

“President Trump has his own unique way of speaking and his unique language,” he said. “We are quite tolerant and expect everyone to be tolerant of us.”