Indeed, an intersting question, which you actually already answered 
yourself. I just tested it myself:

    $ visudo -f /etc/sudoers.d/00-wheel
         %wheel ALL=(ALL) ALL

    $ sudo --list
         User ramon may run the following commands on <some_hostname>:
             (ALL) ALL

    $ sudo -f /etc/sudoers.d/00-wheel
         # negate the entry
         !wheel ALL=(ALL) ALL

    $ sudo --list
         User ramon may run the following commands on <some_hostname>:
             Entry is gone

-Ramon

On 26/10/2022 18:52, Grant Taylor wrote:
> What are end users / systems administrators to do if the default file 
> has something like the following enabled in the default /etc/sudoers 
> file and the EUs / SAs want it to not be there?
>
>    %wheel ALL=(ALL:ALL) ALL
>
> They have no choice but to change (edit / replace) the /etc/sudoers file. 

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