Observers view al-Sharaa's power and influence as more significant than that of the prime minister, who only served in his post for weeks.
Al-Sharaa has more clout as a prominent member of the regime's old guard who served as foreign minister under al-Assad and his late father, Hafez, for more than 20 years.
Andrew Tabler, a Syria expert at the Washington Institute for Near East Policy, said al-Sharaa may have defected "because the battle now has become so sectarian," with an opposition dominated by Sunnis fighting against pro-regime Alawites.
Rafif Jouejati, a spokeswoman for the LCC opposition network, said al-Sharaa's defection could suggest "the regime is collapsing very quickly."
"If confirmed, (this) represents yet another high-level official who sees that the al-Assad regime is a sinking ship," she said. "I expect to see additional defections in both the military and civilian sectors in the coming days."