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The Soroka Medical Centre in Beersheba suffered extensive structural damage following what officials described as a direct hit.
Emergency services treated several people for injuries. The full casualty count remains unclear.
Elsewhere, a separate missile landed near Tel Aviv, damaging a high-rise building and nearby homes.
Israel responded by targeting Iran’s Arak nuclear reactor in a series of airstrikes.
Iran’s foreign minister described the missile attacks as acts of self-defence, with tensions between the two countries now in their seventh day.
