Start of many a Latin American city name NYT Crossword Clue

Think of a holy prefix that blesses many city names in Spanish-speaking regions.

'???' is a Spanish word meaning 'Saint,' often used as a prefix in place names.

The clue refers to the common prefix '???' found in many Latin American city names, such as ??? Juan or ??? José. '???' is the Spanish word for 'Saint,' often used to name cities after saints.

Japanese honorific, With 5-Down, U.S. city with the iconic "crookedest street in the world," as hinted at in the circled letters, Prelude to Antonio or Francisco, The "S" of S.F., ___ Marzano tomato