For the formation of the single NOS, the homolytic dissociation of thio-(hydro)peroxy acid is shown to lead to be a suitable reaction mechanism, avoiding the for-mation of the thermodynamic trap, the sulfinic acid. The double NOS bond formation is then observed to take place through the same reaction mechanism, departing from an already formed single NOS bond and a readily oxidised Cys residue. This carries consequences for the one known system sporting a SONOS bridge, the main protease of SARS-CoV-2. The preference for the single NOS formation with Cys22 is concluded to occur due to higher thermodynamic stability of the reactant state, and could be involved in a conformational change in the second participating cysteine.