Mohamad Chatah, a Sunni official and member of the Future Movement who served as ambassador from 1997 to 1999, was believed to be the target of the bomb, the Los Angeles Times reported. His death was confirmed by the Future Movement, an anti-Hezbollah group supported by Saudi Arabia.
The huge explosion injured about 70 people. Investigators said the bomb may have contained more than 100 pounds of explosive material.
Troops have cordoned off the area near downtown hotels and government buildings, including Parliament.
The attack drew condemnation. Prime Minister Najib Mikati called Chatah a moderate "who believed in dialogue and the language of reason."
No group has claimed responsibility, CNN reported. In a statement on its TV station, Hezbollah said the bombing "only benefits the enemies of Lebanon."
Chatah was a senior adviser to members of the Saudi-backed Future Movement and a confidant of several Lebanese leaders, including former Prime Minister Rafik Hariri, who was assassinated under similar circumstances in February 2005 when his motorcade was hit by a massive bomb.
Chatah, 62, was killed just days before the U.N.-backed Special Tribunal for Lebanon is to begin the trial of four Hezbollah suspects in Hariri's assassination, the (Beirut) Daily Star reported.
A Civil Defense volunteer told the Star most of the victims sustained shrapnel wounds and severe burns.
The Times reported Chatah's apparently last post on his Twitter page, sent shortly before the blast:
"Spillover violence from the Syrian civil war has led to a string of bombings and other attacks in the Lebanese capital. But previous deadly strikes have mainly taken place in the city's Shiite-dominated southern neighborhoods, rather than in the commercial center."
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