Most nauseated with simplest supporting Queen (9)

'most nauseated' is the definition.
('queasy' can be a synonym of 'nauseated')

'simplest supporting queen' is the wordplay.
'simplest' becomes 'easiest' (simple can mean easy or straightforward).
'supporting' says to put letters next to each other (in a down clue, some letters go below others).
'queen' becomes 'qu' (abbreviation for queen).
'easiest' after 'qu' is 'QUEASIEST'.

'with' acts as a link.