Hassan Turkmani, left, Dawoud Rajha, centre, and Assef Shawkat were killed in a bomb explosion at the national security headquarters in Damascus on Wednesday © Reuters

The enemies of Syrian president Bashar al-Assad struck at the heart of his regime on Wednesday when a bomb exploded in the national security headquarters in the heart of the capital, killing at least three top security officials, including the defence minister and Assef Shawkat, the leader’s brother-in-law.

Regime forces hit back within hours to show they were reasserting their authority, using artillery stationed in Jabal Qassioun, overlooking the capital, to shell the Mezze neighbourhood as well as some of the capital’s suburbs.

According to the UK-based Syrian Observatory for Human Rights, which is in contact with a network of activists across Syria, fierce clashes erupted in several neighbourhoods, including Hajar Aswad and Kafar Souseh on the outskirts of the capital, as well as in Midan, one of the first Damascus areas to rise up against the regime.

Activists said government forces were using helicopter gunships and artillery to attack civilian neighbourhoods in an escalation of what rebels have called the battle for the liberation of Damascus. Some rebel commanders said they feared the regime would now use its arsenal of chemical weapons against the people.

Members of the opposition also said they feared the regime’s militia, known as shabbiha, would be sent into Damascus neighbourhoods.

“The shabbiha are everywhere,” said an activist in Yarmouk, a refugee camp near Hajar Aswad. “They are intent on committing massacres.”

The Syrian Revolution General Commission, a network activist on the ground, said pro-Assad thugs had already stormed some rebel areas and were taking their revenge. The report could not be independently verified.

The White House said Mr Assad was losing control of the country. “There is real momentum against Assad, with increasing defections, and a strengthened and more united opposition that is operating across the country,” said Tommy Vietor, a White House spokesman.

“With the Assad regime losing control, it’s time for the Syrian people and the international community to focus on what comes next. We are working urgently with our international partners to push for a political transition in Syria.”

Leon Panetta, US defence secretary, warned the Assad regime it would be held responsible for anything that happened to the country’s large stocks of chemical weapons, which have been a constant source of concern to the international community.

Presidents Barack Obama and Vladimir Putin discussed the situation in Syria in a rare telephone call on Wednesday, even though the Kremlin indicated continued disagreement over how to resolve the crisis.

“Differences in approach remain that concern practical steps in achieving a settlement,” Dmitry Peskov, a Kremlin spokesman, was quoted as saying by Russian news agencies.

Russia’s foreign ministry condemned the assassinations, calling them a “heinous crime” and “another attempt to further destabilise the situation in Syria”. Alexander Lukashevich, a ministry spokesman, said: “Moscow strongly condemns all forms and manifestations of terrorism. We hope the masterminds of the terrorist attack in Damascus will be found and brought to justice.”

Syrian regime officials quickly moved to counter impressions of imminent defeat, saying they would not be deterred in the defence of the nation and what they described as the fight against terrorism.

State television claimed government forces had inflicted heavy casualties on rebels in other parts of the country, and killed commanders. It also interviewed soldiers from Midan, who said: “We will fight till the end, we are still strong and in control of the area.”

The regime blamed the Damascus explosion on a suicide bomber, while opposition activists said it was staged by the rebel Free Syrian Army with help from a regime insider. In an ominous sign for the Assad government, a leading activist said the perpetrator was a bodyguard for a member of the president’s inner circle who had been working with the rebels.

Whoever was responsible, the assassinations underlined the depth of the battle for Damascus and the growing strength of the rebel movement, able to target the president’s closest aides.

“Everyone is scared for what is coming next,” said a diplomat in Damascus. “Because you can’t anticipate what the reaction of the regime will be.”

A new defence minister was quickly appointed after Dawoud Rahja was killed in the explosion. General Hassan Turkmani, a former army chief who is believed to have been part of the core group of security officials fighting the 16-month uprising, was also assassinated.

But it was the demise of Shawkat, the deputy chief of the army and one of the most powerful men in the Assad inner circle, that was considered the biggest blow.

A fourth senior figure, Mohammed Ibrahim al-Shaar, interior minister, was injured. There were conflicting reports on the status of Hisham Bekhtyar, the head of the intelligence services.

Activists said Shami Hospital, where the wounded were treated, had been sealed off by the army.

The whereabouts of Mr Assad himself were unknown but some activists said his brother Maher, head of the elite units of the 4th Division of the army and the Republican Guard – which are responsible for protecting the capital – might have been present at the meeting and could have been wounded.

The explosion followed a rebel attack on an army unit near one of the presidential palaces. Other blasts were reported later in the day near the headquarters of the 4th division, to the south of Damascus.

Analysts cautioned that Wednesday’s events would not bring the immediate collapse of the regime.

Elite military units are tightly controlled by members of the Alawite community, to which the Assad family belongs in a mostly Sunni country, and are likely to strike back hard, possibly exacerbating sectarian tensions in mixed areas in the centre of the country.

But Emile Hokayem, an analyst at London’s International Institute for Strategic Studies, said the attack showed Mr Assad had been decisively weakened and it would thus shake many within the regime who had been waiting to see which side was winning, potentially bringing more defections.

Wednesday’s violence came as world powers, struggling for months to overcome divisions on Syria, delayed until Thursday a vote on a UN Security Council resolution. Western governments want the resolution to include a threat of sanctions if the government fails to abide by a ceasefire and commit to a transition plan.

But Russia, Mr Assad’s chief international supporter, continued to resist the western draft and said the assassinations discredited the case for sanctions.

Sergei Lavrov, Russian foreign minister, said “a decisive battle” was under way in Syria but supporting the opposition was a “dead-end policy”. He added: “Assad will not go on his own and our western partners don’t know what to do about that.”

Speaking against the invocation of Chapter 7 of the UN charter, which authorises the use of force, Mikhail Bogdanov, Russia’s deputy foreign minister, told journalists on Wednesday: “If our western partners could explain how they intend to use the reference to Chapter 7 against those who undertake terrorist attacks, we would be grateful for clearing that up.”

Additional reporting by Charles Clover in Moscow

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