Aleppo, Syria’s second city, could face a catastrophe, triggering massive fresh flows of refugees, unless President Bashar al-Assad and the rebels fighting him agree to freeze the fighting there, the UN special envoy to the war-torn country has warned.

Staffan de Mistura, who has held talks with Assad and the armed opposition, told the Guardian that after the collapse of the Geneva talks earlier this year there was now “no other game in town” for ending a conflict that has cost an estimated 200,000 lives, made millions homeless and destabilised the Middle East since Syria’s uprising at the height of the Arab spring in March 2011.

“At the moment the alternative is simply a continuous conflict in which there is no winner and the only losers are the people of Syria,” the veteran Swedish-Italian diplomat said in an exclusive interview.

Syria’s fractured opposition is deeply uneasy about the idea of a freeze, fearing it will play into Assad’s hands and allow him to free up forces to deploy elsewhere. Monitoring a freeze in an atmosphere of profound mistrust is another issue, as critics of the envoy’s “bottom-up strategy” have cautioned. Sanctions for breaches would be hard to impose unless Russia and Iran, Assad’s allies, were on board.

De Mistura, however, was optimistic. “I have indications that the government of Syria is taking this Aleppo freeze proposal by the UN seriously and that the opposition is seeing that the alternative could be a devastating attack on the city by either the government or by Isis [Islamic State], which is only 22km away. This is based on the concept of giving a moment of hope to the Syrian people and therefore to the international community that there are places where this conflict can be stopped.”

A freeze would also ease delivery of humanitarian aid to the shattered city, whose medieval souk, citadel and great mosque have been destroyed or damaged.

De Mistura’s chances of success may be no greater than for his predecessors, Lakhdar Brahimi and Kofi Annan. But advances by Isis jihadis in Iraq and Syria and the presence of the US-led international coalition fighting them are new factors. Assad is nervous about an extension of the air strikes that have stemmed Isis advances at Kobani on the Syrian-Turkish border, while nationalist rebels with only limited western support fret about being eclipsed by Islamist extremists.

“If the freeze does not take place, Aleppo could be the scene of a catastrophe, with at least 400,000 refugees moving to Turkey and what is left of a unique city, symbolising the many cultures of Syria and the Mediterranean, would become like Homs,” De Mistura said. The old part of Homs, Syria’s third largest city, was all but razed in heavy fighting that ended with a controversial ceasefire earlier this year.

Western governments are being urged to throw their weight behind the initiative, with De Mistura due to brief EU foreign ministers in Brussels on Sunday before a strategy session with the EU’s new foreign policy chief, Federica Mogherini. Diplomats say they hope the EU will back a stabilisation plan for Aleppo and may also appoint a special envoy to Syria.

Another possibility is obtaining the backing of the UN security council for the freeze. That would need the support of Russia and China, which have in the past used their vetoes to protect Assad.

The UN hopes an Aleppo freeze would have a “shock therapy” effect that might galvanise a renewed political effort to end the conflict. But the absence of any immediate prospect of that happening is a source of concern. On Thursday, Britain’s Foreign Office warned: “It is crucial that these efforts are not abused by the brutal Assad regime to inflict more suffering and are part of a broader process that leads to the end to the war in all of Syria.”

De Mistura is based in Geneva but has spent less than a week there since starting work in September, travelling in the Middle East and far beyond. Colleagues praise him as one of the UN’s most capable diplomats who will need to draw on decades of experience to succeed in what has often been called mission impossible.

The envoy declined to divulge the contents of private conversations with Assad, the rebels or other parties but made clear that he and his team had put a huge effort into the current initiative. Nor would he say how long he would persist with it.

De Mistura said he was seeking “a freeze, not a ceasefire, and there is a very big difference. A ceasefire is something that can be broken by one shot, whereas a freeze is an incremental reduction of violence up to the point that everything is completely frozen.” He conceded that the word ceasefire had “an unfortunate connotation in the Syrian context” because some had been achieved by government sieges or starvation so that residents faced no alternative.

“A freeze is when two sides decide to accept a UN proposal for stopping military activities without either side relinquishing their weapons or evacuating the area,” he added. “You just stop fighting. Like in winter, in a freeze there can be moments of heat, but the winter is still there, so the concept is not killed off by inevitable breaches.”