Syrian government forces closed the only road leading into and out of rebel-held parts of the northern city of Aleppo on Sunday, besieging hundreds of thousands of people and giving President Bashar Assad's forces one of their biggest successes since the five-year conflict began.

Sunday's push raised fears among the city's civilian population of a humanitarian crisis as many feared food and medicine will run out in Aleppo within a short time.

The siege marks the biggest victory for the government in Aleppo since rebels captured parts of the city in the summer of 2012. Aleppo, Syria's former commercial center and the country's largest city, has been divided and contested since then.

Aleppo and its suburbs have seen intense fighting in recent months, with Syrian troops and their allies advancing with the aid of Russian airstrikes. Earlier this year the government launched a large-scale offensive that captured much of the city's northern outskirts.

The capture of the road came as Russia and the United States, who support rival parties in the conflict, are negotiating a possible military partnership over Syria. Both countries have been trying to end the conflict in Syria, now in its sixth year.

An eventual government victory in Aleppo would be a major turning point in the conflict in favor of Assad.

The Britain-based Syrian Observatory for Human Rights said government forces and members of Lebanon's Hezbollah group reached the Castello road early Sunday, closing it and raising fears of a humanitarian crisis. Government forces reached a point where they could fire on the road earlier this month, effectively cutting it off, though some people still made the dangerous journey.

"Aleppo is under full ground siege after the regime took some points on the road," Aleppo-based activist Bahaa al-Halaby told The Associated Press by telephone. He added that as of Sunday, food and medical supplies will not be able to reach rebel-held parts of the city and seriously wounded people will not be taken for treatment in other parts of northern Syria or Turkey.

The Observatory said 16 militants were killed in Sunday's fighting alone.

The Observatory's chief Rami Adurrahman said government forces are still pushing to gain more ground around the Castello road in order to make it difficult for any rebel counteroffensive to open the road into the city again.

"This is a decisive battle and could turn the war in favor of the regime," Abdurrahman said.

Five years of conflict have killed more than a quarter-million people, created Europe's biggest refugee crisis since World War II and allowed the Islamic State to carve out its own territory across parts of Syria and neighboring Iraq.

The United Nations says there are nearly half a million people in besieged areas in Syria and an estimated 4.5 million Syrians are in a separate category called "hard to reach."

The U.N. warned earlier this month that nearly 300,000 people rely on the Castello road for travel, food and medicine.

Another activist based in Aleppo said the city is being subjected to intense shelling and airstrikes. Baraa al-Halaby, who is not related to Bahaa, said vegetable and fruit markets were almost empty on Sunday morning and that residents were lining up outside bakeries.

"Humanitarian conditions are difficult," he said.

The siege on rebel-held parts of the city came hours after mysterious explosions rocked the so-called Defense Factories, a sprawling government military facility outside the town of Safira just south of Aleppo.

The Observatory said the cause of the explosions is not clear, but that they killed at least 10 people and caused heavy damage.

State news agency SANA said the explosions were caused by a technical failure. It did not elaborate.