Syrian rebels cut the Damascus to Aleppo highway on Thursday as fighting with regime forces killed around 200 people, including civilians hit by Russian air force strikes.
A day earlier, the hardline Islamist group Hayat Tahrir al-Sham (HTS), which dominates rebel-held northwest Syria and allied factions launched a surprise attack on government-held areas of northern Aleppo province, triggering the fiercest fighting in years, the Syrian Observatory for Human Rights said.
The toll in ongoing battles "has risen to 182, including 102 fighters from HTS", 19 from allied factions "and 61 regime forces and allied groups", said the Observatory.
"Russian air strikes on the Aleppo countryside killed 19 civilians on Thursday," said Rami Abdel Rahman, who heads the Observatory, adding that another civilian had been killed in Syrian regime shelling a day earlier.
Russia is a close ally of Syrian President Bashar al-Assad and first intervened in Syria's civil war in 2015, turning the momentum of the conflict in favour of the president, whose forces once only controlled a fifth of the country.
HTS and its allied factions, including groups backed by neighbouring Turkey, "cut off the Damascus-Aleppo international M5 highway... in addition to controlling the junction between the M4 and M5 highways," said the Britain-based monitor.
"The highway has now been put out of service, after it was reopened by regime forces years ago," said the monitor, which has a network of sources inside Syria.
The junction of the M5 and M4 highways connects the capital and regime coastal stronghold Latakia with second city Aleppo respectively.
The Syrian conflict broke out in 2011 after the Assad regime brutally suppressed peaceful protests calling for democracy.
Over 500,000 people have been killed, mostly as a result of regime bombardment of civilian areas and millions more displaced, and the conflict has drawn in foreign countries and jihadist groups. However, the intensity of the conflict had decreased in recent years.
Some of the clashes, which are happening in an area straddling Idlib and Aleppo provinces, are less than 10 kilometres (six miles) southwest of the outskirts of Aleppo city.
"This operation aims to repel the sources of fire of the criminal enemy from the frontlines," said Mohamed Bashir, who heads HTS's so-called "Salvation Government", during a press conference.
Analyst Nick Heras of the New Lines Institute for Strategy and Policy said the rebels were "trying to preempt the possibility of a Syrian military campaign in the region of Aleppo, which Russian and Syrian government airstrikes against rebel areas has been preparing for".
With some Turkey-backed factions joining the offensive, he said "Ankara is sending a message to both Damascus and Moscow to back down from their military efforts in northwest Syria," he said.
As well as Russia, Syrian President Bashar al-Assad has been backed in the civil war by Iran and allied militant groups, including Lebanon's Hezbollah.
A general in Iran's Revolutionary Guards was killed in Syria on Thursday during fighting between Syrian regime forces and rebels, an Iranian news agency reported.
During more than two months of war with Hezbollah in Lebanon, Israel intensified its strikes on Iran-backed groups in Syria including Hezbollah.
Rebel forces "are in a better position to take and seize villages than Russian-backed Syrian government forces, while the Iranians are focused on Lebanon," Heras said.
The Syrian rebels launched their attack the day the Lebanon-Israel truce came into effect.
Analyst Haid Haid said the rebels had been "planning for this offensive for quite a while".
But "if the rebel forces waited too long the regime would have been able to reinforce their frontlines as Hezbollah forces are no longer busy with the war in Lebanon".
HTS, led by Al-Qaeda's former Syria branch, controls swathes of the northwest Idlib area as well as small parts of neighbouring Aleppo, Hama and Latakia provinces.
An AFP correspondent reported heavy, uninterrupted clashes east of the city of Idlib since Wednesday morning, including air strikes.
A military statement carried by state news agency SANA said that "armed terrorist organisations grouped under so-called 'Nusra terrorist front' present in Aleppo and Idlib provinces launched a large, broad-fronted attack" on Wednesday morning.
It said the attack with "medium and heavy weapons targeted safe villages and towns and our military sites in those areas".
The army "in cooperation with friendly forces" confronted the attack "which is still continuing", inflicting "heavy losses" on the armed groups, the military statement said, without reporting army losses.
Prior to the rebel-held offensive, the Idlib region was subject to a ceasefire - repeatedly violated but which had largely been holding - brokered by Turkey and Russia after a Syrian regime offensive in March 2020.