A string of bomb attacks on Sunday near a Shiite shrine south of Damascus which killed 120 people in total was the deadliest attack since Syria's war erupted in 2011, a monitor said.
At least 90 civilians were among those killed when suicide attacks claimed by the Islamic State jihadist group (ISIS) ripped through the area of the Sayyida Zeinab shrine, the Syrian Observatory for Human Rights said.
They included displaced people from other parts of Syria, devastated by a nearly five-year conflict.
The rest of the dead were from pro-regime security forces, according to Observatory head Rami Abdel Rahman.
The bloodiest attack before Sunday's explosions had been carried out by Al Qaeda's Syrian affiliate, Al Nusra Front, in May 2012 near Damascus and had killed 112 people.
Sunday's blasts drew sharp condemnation from UN special envoy for Syria Staffan de Mistura.
An AFP reporter at the scene said the explosions struck about 400 meters (yards) from the revered Shiite shrine containing the grave of a granddaughter of the founder of Islam Mohammed.
A January attack in the same area – also claimed by ISIS – killed 70 people.
Sunday's attack on the shrine came on the same day as a separate bomb attack – also claimed by ISIS – struck the regime-held Al-Zahraa district of Homs, killing at least 59 people.
ISIS surprise attack captures key regime position
It was followed on Monday by news that ISIS and other jihadists had cut a vital supply route linking the west of Syria's second city Aleppo with other government-held territory.
The road between Aleppo and the town of Khanasser to the southeast was the only way regime forces and civilians living in government-controlled neighborhoods of the city could travel to surrounding provinces.
If government forces are unable to recapture the road, it could slow an offensive they launched in the countryside around Aleppo earlier this year, and could worsen severe shortages of food and water for civilians.
"Jihadists from the Caucasus and from (China's mainly Muslim region of) Xinjiang, as well as the jihadist group Jund al-Aqsa, cut the route from the south after a surprise attack," said Syrian Observatory for Human Rights chief Rami Abdel Rahman.
"And fighters from IS cut off a different part of the route from the northern side at the same time," Abdel Rahman said.
Thousands of foreign fighters have flocked to Syria over the past two years, many of them taking up arms with Al-Qaeda affiliate Al-Nusra Front, ISIS or Jund al-Aqsa.
It is not the first time that the regime's supply route to Aleppo has been cut.
Rebel cut it in 2013 and ISIS did so last year before being pushed back.
The new setback comes with government troops on the offensive north and west of Aleppo, where rebel forces in the east of the city are almost completely surrounded.
The violence comes as efforts intensified for a partial truce in Syria, and as fighting raged near Aleppo on Monday.
US President Barack Obama and Russian counterpart Vladimir Putin are expected to speak in the coming days after Washington announced a provisional agreement had been reached on an imminent "cessation of hostilities."
US Secretary of State John Kerry announced the deal on Sunday, as the string of suicide bombings in Damascus and Homs left at least 179 people dead.
Kerry said the US and Russian leaders were to speak "in the next days or so" on the terms of implementing the agreement, which would apply to fighting between non-jihadist rebel forces and regime troops backed by Moscow and Tehran.
The partial ceasefire would not extend to international efforts to combat ISIS and other jihadist groups in Syria, complicating its implementation. Among the groups classified as "jihadists" by both the US and Russia is Al Qaeda's Nusra Front, which is at the forefront of rebel operations in northern Syria and has cultivated a network of allied Islamist brigades.
Announced by top diplomats in Munich earlier this month, the ceasefire failed to take hold by last Friday as initially planned.
Opposition talks in Riyadh
Part of a plan that also included expanded humanitarian access, the proposal aims to pave the way for a resumption of peace talks that collapsed earlier this month in Geneva.
The talks had been scheduled to resume on February 25, but the UN Syria envoy has already acknowledged that date is no longer realistic.
Syria's main opposition umbrella group, the High Negotiations Committee (HNC), was meeting in the Saudi capital Riyadh on Monday for talks on the ceasefire and peace talks efforts.
Spokesman Monzer Makhous told AFP the meeting was expected to continue for two or three days.
The HNC has said any ceasefire must include provisions for Russia, Iran and foreign militia forces backing the regime to stop fighting.
Russia launched air strikes in Syria last September against what it said were "terrorists" but has been accused of bombing non-jihadist rebel forces in support of President Bashar al-Assad, a longtime ally.
Iran has sent military "advisers" to Syria – including thousands of Revolutionary Guards fighters and other "volunteers" – and the Tehran-backed Lebanese Shiite movement Hezbollah has deployed at least 6,000 terrorists to fight with Assad.
Iran would have to be on board for any ceasefire to work and Russian Defense Minister Sergei Shoigu made a surprise visit to Tehran on Sunday, saying he was delivering a "special message" from Putin to President Hassan Rouhani.
Efforts have been intensifying to resolve Syria's war – which has left more than 260,000 dead, forced millions from their homes and devastated the country – as the conflict approaches the five-year mark in March.
The rise of ISIS, which has seized large parts of Syria and neighboring Iraq and become the preeminent global jihadist group, has focused attention on the need for a solution.
Key supply route cut
Assad's forces have been making important gains since the start of Russian air strikes, with particularly heavy fighting in recent weeks around the second city of Aleppo that has sent tens of thousands fleeing to the Turkish border.
But their efforts to take Aleppo city – long divided into regime- and rebel-held areas – were dealt a setback on Monday.
ISIS and other jihadists cut a vital supply route linking the west of Aleppo with other government-held territory, the Observatory said.
The road between Aleppo and the town of Khanasser to the southeast was the only way regime forces and civilians living in government-controlled neighbourhoods of the city could travel to surrounding provinces.
If government forces are unable to recapture the road, it could slow their offensive in the area.
AFP contributed to this report.