A landmark partial ceasefire -- not including the Islamic state group -- which was negotiated by the United States and Russia and took effect on February 27, had dramatically curtailed violence across much of Syria and raised hopes that a lasting deal could be struck in Geneva to end the bloodshed.
But the country has been rocked by fighting in recent weeks, particularly around the city of Aleppo, where at least 25 civilians were killed and 40 wounded in air strikes on rebel-held neighbourhoods on Friday alone, emergency workers said.
- Fragile peace talks -
De Mistura said Friday's violence in Aleppo was "very worrisome".
Frustrated by the surging violence, the lack of access for desperately needed aid and the failure to secure the release of detainees, Syria's main opposition High Negotiations Committee (HNC) halted its formal participation this week in the Geneva talks.
But de Mistura said Friday that members of his team had continued to hold "very, very productive" meetings at a technical level with remaining HNC members at their Geneva hotel.
And he said he intended to push ahead with the ongoing round of talks, which began on April 13, until Wednesday.
"We need to try until Wednesday to get as deep as possible... and we can do that both formally, informally, technically, practically," he said.
He hailed all sides finally engaging in discussions on the thorny issue of political transition, but acknowledged that the understanding of what that would entail still differed widely.
The fate of President Bashar al-Assad remains a major sticking point in the indirect talks, with the opposition insisting any peace deal must include his departure, while Damascus insists his future is non-negotiable.
The HNC, an umbrella group comprising the main Syrian opposition and rebel factions that came together in Riyadh in December, said in a statement Friday that it was continuing "to work hard for progress on political transition, for relief from sieges and air strikes".
"And we have had a meeting here today on the detainee issue," it said, stressing that it considered the ceasefire to be "in trouble".
HNC spokesman Salem al-Meslet told AFP that if the group sees "major and serious steps on the ground... in the next couple of days, there will be nothing stopping the members who left Geneva from returning".
- 'Murderous regime' -
De Mistura called for a new high-level meeting of the 17-country International Syria Support Group, which is co-chaired by the United States and Russia.
"We do need certainly a new ISSG at the ministerial level, because the level of danger... (means that such a meeting) is urgently required," he said.
Obama meanwhile lashed out at Moscow for supporting "a murderous regime", but vowed to keep working with the Russian government to strengthen the ceasefire and support the peace talks.
He said he had spoken to Russian President Vladimir Putin on Monday "asking him to put more pressure on (Syrian President Bashar al) Assad, indicating to him that we would continue to try to get the moderate opposition to stay at the negotiating table in Geneva".
"If in fact the cessation falls apart, we will try to put it back together again even as we continue to go after ISIL," he said, referring to IS, which along with other jihadists is not included in the truce deal.
The group said it had captured a Syrian pilot alive on Friday after shooting down his plane east of Damascus.
Since Syria's conflict erupted in March 2011, more than 270,000 people have died, according to the Syrian Observatory for Human Rights, which is considered to have the most reliable count.
The UN no longer provides casualty figures for Syria, since it considers them too difficult to verify, but de Mistura said Friday he believed the actual toll had to be far higher, likely around 400,000.
The Pentagon meanwhile said 20 civilians had been killed in US airstrikes on IS targets in Syria and Iraq over a five-month period, although observers warned the toll is likely much higher.