GAZIANTEP, Turkey — A growing chorus of alarm has warned the Obama administration that its strategy to combat Islamic State forces in Syria is on the verge of unraveling in Aleppo, Syria’s second-largest city. But with regime forces now in control of all but one road into Aleppo, the remaining residents of areas controlled by the rebels designated “moderate” by the U.S. are bracing for the worst.

“We started planning for the siege,” Zaina Erhaim, a journalist living in Aleppo, told Al Jazeera. "I have a friend who is a theater director who is learning how to use a pump action [shotgun]. If the regime attacks the city, he’d have to defend himself.”

Forces fighting for the regime of President Bashar al-Assad have taken advantage of the U.S.-led air campaign against Islamic State of Syria and the Levant (ISIL) targets elsewhere in Syria to press their offensive in Aleppo and are now within firing range of Castello Road, the rebels’ last remaining supply route. “They can close it whenever they like,” Erhaim said, speaking by phone. “Maybe they’re still opening it for those who want to escape, before applying the siege.”

Aleppo is the most significant real estate to fall into rebel hands in the course of Syria’s three-year civil war, and the rebel sectors are under the control of forces designated as the Syrian partners vital to the U.S. campaign there. Earlier this year, fighters from three rebel alliances successfully forced ISIL to the periphery of the city while holding off the regime army. But the threat of a regime encirclement of the city represents a turning point in the multipolar fight in Syria among rival rebel factions, Assad’s forces, the Qaeda-affiliated Jabhat Al-Nusra (the Nusra Front) and ISIL — a fight in which the rebel forces designated as potential partners by the West are rapidly being eclipsed. French Foreign Minister Laurent Fabius warned earlier this week that the “moderate” rebels are at risk of being obliterated if they lose their Aleppo foothold.

“The combined real and psychological impact of regime success in initiating a siege would amount to an unprecedented blow to the viability of rebel factions in Aleppo,” said Noah Bonsey, a senior analyst on Syria at the International Crisis Group. “[ISIL] can be expected to exploit rebel focus on preventing besiegement by escalating its own campaign to capture valuable rebel-held territory along the Turkish border north of Aleppo.”

Taking advantage of the international focus on the dramatic battle for the Kurdish town of Kobane, along the border with Turkey, the Assad regime has pressed to recover lost ground on other fronts. During one 36-hour period in October, the Syrian military carried out more than 200 airstrikes in rebel-held areas throughout the country, according to the watchdog group Syrian Observatory for Human Rights.

Syrian regime warplanes are pummeling the rebel-controlled north even as U.S. planes fly sorties in Syrian airspace to target ISIL and Jabhat Al-Nusra. Residents, activists and armed groups that are fighting both ISIL and Assad are outraged by the hands-off approach of the U.S. to regime attacks.

“They’re extremely pissed off,” said Assaad al-Achi, an opposition politician who moves in and out of northern Syria. On a recent visit to the town of Saraqib, he said he witnessed anti-ISIL rebels shooting at a U.S. drone. He feared U.S. retaliation. “We spent all night waiting for the Tomahawk,” he said.