Direct flights start between Israel’s Tel Aviv and Egypt’s Sharm el-Sheikh
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Flight 5193, operated by El-Al subsidiary Sun d'Or, departed Ben Gurion International Airport at 0715 GMT, the carrier said in a statement.
The two countries have lately bolstered their ties.
Israeli Prime Minister Naftali Bennett has twice visited Egypt after coming to power in June, and met President Abdel Fattah al-Sisi in September.
Prior to that, Egyptian flights to Israel had been operated by an Egyptair subsidiary, Air Sinai, set up exclusively for the Israeli route and without displaying the Egyptian flag on the exterior of its planes.
Some in Egypt continue to oppose ties with the Jewish state.
The Egyptian branch of the Boycott, Divestment and Sanctions movement, which opposes Israel's occupation of Palestinian territories, has called for a boycott of two Israeli-organised dance festivals due to take place in Sinai over the coming days.
That year, they were joined by Bahrain, Morocco and the United Arab Emirates, which all now operate direct flights to the Jewish state.