Saudi Arabia, which is hosting the yearly summit in the Eastern Province city of Dhahran, is likely to seek Arab support to pile the pressure on Iran, analysts say.
"The Saudis are going to push for a much harsher stance on Iran -- not necessarily on the nuclear dossier per se, but on Iranian influence in the Arab countries, particularly Iraq, Syria, Lebanon and Yemen," said Karim Bitar of the Paris-based Institute of International and Strategic Affairs.
Iran's influence is wielded through a land route of armed parties in the Middle East -- the so-called "Shiite crescent" that cuts across the mainly Sunni Arab world.
Iran also openly supports the Shiite Huthi rebels in Yemen in their war against the Saudi-backed government but denies accusations of smuggling arms to the insurgents.
And in Shiite-dominated Iraq, the Islamic republic backs armed groups and supports the government.
"The securitisation of Iran is being pushed predominantly by Saudi Arabia and the UAE, along with other Arab countries including Egypt," said Andreas Krieg, assistant professor of defence studies at King's College London. "Saudi Arabia has also reached out to Iraq to try and build ties and tackle militias there," Krieg told AFP.
"It's definitely safe to say that Iran is the centrepiece of this summit."
The summit will be attended by delegations from 21 of the Arab League's 22-member states. Syria has been suspended from the organisation for seven years over Assad's crackdown on protesters.
Trump has put off a final decision on US-led strikes against Syria after an alleged chemical attack against the rebel-held town of Douma that killed dozens. The summit is expected to release a statement on the suspected toxic gas attack, but it remains to be seen whether the Arab League will take any action as well. Syria serves today as a major pivot between Saudi Arabia and its allies on the one hand, and Iran and Hezbollah on the other.
Each party in the conflict backs opposing sides but all agree that the country's future cannot be decided solely by the Assad regime, whose troops have regained territory with Russia's support.
After years of demanding that Assad step down, Saudi Arabia this month conceded, in the words of its powerful crown prince, that the embattled president was staying.
"Certain regional powers previously determined to bring down the Syrian regime -- particularly Saudi Arabia and Turkey -- have now accepted the status quo, that Assad is staying," Bitar said.
"Bashar's Iranian patrons are also very well aware that their protege cannot run the show on his own and they are starting to accept the premise that they will have to negotiate spheres of influence in Syria territories".
Not on the table at the summit, according to Krieg, is Qatar, cut off from its Gulf allies over accusations of ties to Iran and support for Islamist extremists -- claims denied by Doha.
The summit also comes after 33 Palestinians were killed and hundreds wounded at the hands of Israeli forces in mass protests along the Gaza border in recent weeks.
The protests are to continue until mid-May, around the time Washington is to move its embassy to Jerusalem, which both Palestinians and Israelis claim as their capital.
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