The formation of such a cross-link requires the oxidation of both Cys and Lys residues. Cys residues are broadly known to oxidize through the thiol moiety leading to a wide variety of oxidation products such as the thiyl radical, the disulfide bond or the sulfenic or sulfinic acids. In this vein, an antioxidizing character is commonly attributed to the thiol moiety, due to its ability to quench oxidizing species. A clear biological example being the Glutathione, a tripeptide found in different organisms, protecting them against oxidation. On the other hand, Lys residues are less susceptible to oxidation and in case of oxidation, the formation of carbonyl groups have been reported. It is therefore surprising to observe a cross-linker formed by these pair of residues. At first, the formation of single NOS bridges was reported. However, it has recently been shown that further oxidation of the amino moiety of the Lys is possible in the main protease of SARS-CoV-2 (M P ro ), leading to the formation of a double NOS bridge (SONOS). It has also been observed that NOS bonds can be formed both in the presence of molecular oxygen and hydrogen peroxide in solution, the latter being somewhat faster. The exact identity and the breadth of reactive oxygen species (ROS) which can bring about the reaction are unknown, given that the chemistry of ROS in water are quite intricate. Take for example the recent discovery of spontaneous hydrogen peroxide formation in water microdroplets. We decided to focus foremost on three potential agents -hydrogen peroxide, triplet and singlet molecular oxygen -which we hope will be representative. We extended this list including obvious suspects such as the superoxide anion (O •- 2 ) and the derivatives that may arise from the decomposition of hydrogen peroxide, e.g. the hydroxyl radical ( • OH), the hydroperoxyl radical ( • OOH) and the hydronia radical (•H 3 O). On the homolytic dissociation of H 2 O 2 , the formation of •OH was reported to be around 50 kcal/mol in gas phase, and in water the bond was shown to be 2-5 kcal/mol weaker. Recently, calculations have put forward that in solution hydrogen peroxide can dissociate to •OH or •OOH and •H 3 O with activation barriers of 11.3 kcal/mol and 8.2 kcal/mol respectively, making these species somewhat accessible. The study of the decomposition mechanism of H 2 O 2 in water and the review of these values is beyond the scope of the current work, as we will focus primarily on the oxidation of the target residues. Albeit pertinent, it is extremely intricate to clearly identify the ROS responsible for the reaction. The intermediates considered in this study should be taken as potential radical species which promote the oxidation of Cys and Lys residues.