The Damascus strike is being viewed by observers as the buildup of hostilities in the middle east as Israel's war with Hamas has entered the fourth month.

The alleged strike targeted the Mazzeh neighborhood in Syria's capital, where several diplomatic missions including the Iranian embassy, are located, according to Syrian authorities.

Israel "launched an air attack from the Golan Heights at 10:20 a.m. local time that targeted a residential building in the Mazzeh neighborhood," the Syrian Ministry of Defense alleged, adding that some missiles were shot down by national defense forces.

Numerous buildings and adjacent vehicles were damaged in the blast, Syria's state broadcaster reported, with civil defense teams still searching for victims trapped under the rubble.

The Israel Defense Forces declined to comment on the incident, telling CNN, "We do not comment on foreign reports."

One of the dead, Hojjatollah Omidvar, was described by Iran’s semi-official Student News Network as a deputy chief of the Quds Force intelligence unit in Syria - one of five branches of the Revolutionary Guards unit in charge of foreign operations.

The Islamic Revolutionary Guard Corps (IRGC) identified the four others killed as military advisors Ali Aghazadeh, Hossein Mohammadi, Saeed Karimi and Mohammad Amin Samadi. Their presence in Syria had been "at the official invitation of the Syrian government", Iranian foreign ministry spokesperson, Nasser Kanaani, noted in a statement on social media.

The Damascus missile hit raises concerns that Israel's war with Hamas in Gaza is spiraling into a regional war. In northern Iraq, an Iranian missile attack last week targeted what Tehran claimed to be a spy base for Israeli intelligence agency Mossad.

In Lebanon, militant group Hezbollah has engaged in near-daily confrontations with Israeli forces across the border. And from Yemen, Houthi rebels have launched a series of attacks on commercial ships and Western military vessels in the Red Sea, media reports said.

Attacks by Iranian-backed groups in the Middle East won't stop until Israel's war on Hamas in Gaza ends, Tehran's top diplomat warned on Wednesday, echoing comments by several groups in Iran’s network of influence.

"If the genocide in Gaza stops, then it will lead to the end of other crises and attacks in the region," Iranian Foreign Minister Hossein Amir-Abdollahian told CNN in an interview at the World Economic Forum in Davos on Wednesday.

Since Israel launched its ground and air campaign in Gaza, in response to Hamas' October 7 terror attacks, nearly 25,000 people have been killed in the blockaded Palestinian enclave – the majority of them women and children - according to the Palestinian Ministry of Health in Ramallah.

The US, a key Israel ally, launched strikes in Yemen to degrade Houthi capabilities to harm the vital Red Sea shipping lane. In comments on Wednesday, State Department spokesperson Matt Miller emphasised that a larger conflagration could be avoided and highlighted a flurry of US diplomatic activity in the Middle East.

"We continue to engage in diplomatic efforts to try to make clear to everyone in the region that we don’t want to see the conflict escalated, that we don’t think it’s in any country’s interest to see the conflict escalated," Miller said on Wednesday.

The de-escalation path appears elusive as Iranian president Ebrahim Raisi on Saturday vowed to "punish" Israel for the Damascus missile strike.

The killing was "another stain on the record of all governments who claim to be the advocates of human rights because it violated Syria’s airspace and trampled on human and international laws", he said, in comments reported by Iranian state media.