Damascus/Washington - At least 60 people were killed and dozens wounded on Sunday by a car bomb and two suicide bombers in a district of Damascus where Syria's holiest shrine is located.

Syria's main opposition group met UN mediator Staffan de Mistura for the first time on Sunday, but the talks ran straight into trouble after the bombings.

Islamic State claimed responsibility for the attacks, according to Amaq, a news agency that supports the group. It said two operations "hit the most important stronghold of Shi'ite militias in Damascus".

The Syrian Observatory for Human Rights said the casualties were expected to rise from the suicide attacks in Sayeda Zeinab, a district of southern Damascus where the Lebanese militant group Hezbollah and other Iraqi and Iranian militias have a strong presence.

Sayeda Zeinab, south of Damascus, contains the grave of a granddaughter of Prophet Muhammad (PBUH) and is particularly revered as a pilgrimage site by Shiites. It has continued to attract pilgrims from Syria and beyond, particularly Shiites from Iran, Lebanon, and Iraq, throughout the nearly five-year war.

In Geneva, representatives of the Saudi-backed Higher Negotiation Committee (HNC) - which includes political and militant opponents of President Bashar al-Assad - warned they may yet walk away from the talks unless the suffering of civilians in the five-year conflict is eased.

The head of the Syrian government delegation retorted that the blasts in Damascus, which the Interior Ministry blamed on a car bomb and two suicide bombers, merely confirmed the link between the opposition and terrorism - even though Islamic State has been excluded from the talks.

The United Nations is aiming for six months of negotiations, first seeking a ceasefire, later working toward a political settlement to the civil war that has also killed over 250,000 people, driven more than 10 million from their homes and drawn in global powers.

Only on Friday, the HNC said it would boycott the process, insisting it wanted an end to air strikes and sieges of Syrian towns before joining the negotiations. This forced de Mistura - who invited the government and opposition umbrella group for "proximity talks", in which he would meet each side in separate rooms - to set the ball rolling with only the government delegation.

Under intense pressure, the HNC later relented and arrived in Geneva on Saturday. However, the group questioned how long the delegation would stay.

"In view of the (Syrian) regime and its allies' insistence in violating the rights of the Syrian people, the presence of the HNC delegation in Geneva would not have any justification and the HNC could pull its negotiating team out," the group's coordinator, Riad Hijab, said in an online statement.

In Washington, US Secretary of State John Kerry urged Syria's government and opposition groups to "seize the opportunity" to participate in UN-sponsored peace talks, emphasizing that there is no military solution.

"This morning in light of what is at stake in these talks, I appeal to both sides to make the most of this moment, to seize the opportunity for serious negotiations, to negotiate in good faith with the goal of making concrete measurable progress in the days immediately ahead," Kerry said.

Ahead of making the statement, Kerry spoke to Russian Foreign Minister Sergei Lavrov by telephone on Saturday to review the situation.

Kerry said "The bloodshed will drag on without negotiations. That will ensure an increased number of terrorists."

Kerry encouraged the opposition groups and government — whom have been asked by UN mediators to meet in separate "proximity talks" — to "make the most of this moment."

An AFP photographer said the Sunday’s explosions in Damascus damaged the facade of a nearby building, scorching all of its six storeys. In the aftermath of the attack, smoke rose from the twisted carcasses of more than a dozen cars and a bus, as ambulances ferried away the wounded and firefighters worked to put out blazes.

State television showed footage of burning buildings and wrecked cars in the neighbourhood.

Syrian state news agency SANA, quoting an interior ministry source, said a group of militants had detonated a car bomb near a public transport garage in the neighbourhood's Koua Sudan area. Two suicide bombers then blew themselves up nearby as people were being rescued.