The Damascus bombing killed or severely injured four out of about eight of Bashar al-Assad's inner circle, who have been responsible for directing the bloody crackdown since the start of the uprising.
One of the dead – Assef Shawkat, the President's brother-in-law and head of his crisis team – had been blamed for some of the most brutal episodes of repression. Born in 1950 to a middle-class Alawite family, Shawkat studied law in Damascus before joining the military in the late 1970s. He rose quickly through the ranks and was described by colleagues as an ambitious man. His marriage to Bushra, daughter of the then-President Hafez al-Assad, helped him to rise further still and allowed him to form a close relationship with Bashar al-Assad.
When Assad became President, Shawkat was appointed the de facto chief of military intelligence, a title he officially acquired in 2005, making him a key member of the regime's inner circle and a pillar of the Assad family's rule.
The Interior Minister, Mohammad Ibrahim al-Shaar, who, according to differing reports was either killed or critically wounded, and Hisham Ikhtiyar, the injured national security chief, were said to have been in charge of compiling lists of opposition figures. Shaar, an Alawite, was appointed Interior Minister in a cabinet reshuffle in April last year. He previously held a number of security posts, including head of the military police. He was among members of Assad's inner circle who were targeted by EU sanctions in May 2011.
Also killed was Dawoud Rajha, the Defence Minister, a Greek Orthodox Christian whose presence in the cabinet was meant to show inclusiveness in Syria's Alawite-dominated hierarchy. Appointed in August 2011 after serving as army chief of staff for two years, he had also become an important conduit to the Russian government.
The third fatality was General Hassan Turkmani, a former Defence Minister and current assistant to the Vice-President. He was not regarded as being among Assad's close confidants.
Those surviving members of the President's close-knit circle include his brother Maher, commander of the army's 4th Division, whose troops have been accused of abuses and arbitrary killings. He was briefly reined in by Assad, but has risen in influence with the surge in violence.
General Ali Mamlouk, the chief of general intelligence, Abdel-Fattah Qudsiyeh, the head of military intelligence, and Mohammed Nassif Kheyrbek, a security adviser, are the others who can be expected to play leading roles for however long the regime continues to last.
General Fahd Jassim al-Furayj was appointed Defence Minister within hours of the bombing.