Replace [^a-zA-Z0-9 -] with an empty string.

Regex rgx = new Regex("[^a-zA-Z0-9 -]");
str = rgx.Replace(str, "");

So there are following things which are wrong in your pattern, let's address them first

• A-z - It includes all the character from ascii table starting from A to z, which also has non alphabetical characters which we don't want to match, so the correct one should be [A-Z] if we want only uppercase, if we want both upper and lowercase then it should be [A-Za-z] or you can turn on i flag
• ^\s - ^ means negation only when you use it as first character inside the character class elsewhere it is treated as literal ^

So your regex should be

 [^A-Za-z\s]

The [..] form is known as a collection (:h /[]) and can contain a sequence of characters and/or one or more ranges of characters, separated with -. It will match any single character that is contained in the sequence/range(s). You can, of course, also match the inverse with ^.

In :h white-space you'll find a collection equivalent to \w:

\w  word character:         [0-9A-Za-z_]

So one approach is to invert/negate that equivalent:

[^0-9A-Za-z_]

Alternatively, collections can also contain the "character classes" found under :h E944. These are the same character classes that have been around forever in the BRE/ERE patterns used by legacy tools and POSIX environments.

Alphanumeric chars have the following character class equivalent:

[:alnum:]   isalnum ASCII letters and digits

You can invert/negate that like so:

[^[:alnum:]]

(You could also probably use negative lookarounds with \w but that's relatively difficult compared to this straightforward analog to [^\w].)

Update: I just realized I didn't address the full pattern you posted. Just look for a character class that's equivalent to \s and you'll find [:space:]. And " is just ". So [^\w\s"] becomes:

[^[:alnum:][:space:]"]

One other thing, this is likely to be the most performant of any possible solutions since others have lookarounds or alternations (|) and those are expensive.

To match anything other than letter or number you could try this:

[^a-zA-Z0-9]

And to replace:

var str = 'dfj,dsf7lfsd .sdklfj';
str = str.replace(/[^A-Za-z0-9]/g, ' ');

It can't be done in one pass.
Here is a way to do the job with multiple passes:

• Ctrl+H
• Find what: ^([^a-z0-9;:]*)([a-z0-9]*)(?1)(.*?[;:].+$)
• Replace with: $2$3
• Uncheck Match case
• check Wrap around
• check Regular expression
• DO NOT CHECK . matches newline
• Replace all (Click here as many times as needed, it replaces only a part of invalid characters each time)

Explanation:

^                   : begining of line
  (                 : start group 1
    [^a-z0-9;:]*    : negative character class, 0 or more any character that is not alpha-num or colon or semicolon
  )                 : end group 1
  (                 : start group 2
    [a-z0-9]*       : character class, 0 or more alpha-num
  )                 : end group 2
  (?1)              : re-use the pattern in group 1 (ie. [^a-z0-9;:]*)
  (                 : group 3
    .*?             : 0 or more any character but newline, not greedy
    [;:]            : a colon or semicolon (the first that exists in a line)
    .+              : 1 or more any character but newline (the password)
    $               : end of line
  )                 : end group 3

Replacement:

$2      : content of group 2, the alpha-num part of the name
$3      : content of group 3, rest of the line

Result for given example:

start1:stop.~1@
Stars:B!ge(s+R}\
Step14:St,./\Ert`               <== I guess there is a typo in your request
username:P@$$wor'";D
Test;pass;word123
username;password!#$~`'123
45Star5Lord1:@T1esting!
usernametest:Pa:ssw/orD$+;