Novel coronavirus disease 2019 (COVID-19) has resulted in a global pandemic and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have suggested that a precise disulfide-thiol balance is crucial for viral entry and fusion into the host cell and that oxidative stress generated from free radicals can affect this balance. Here, we reviewed the current knowledge about the role of oxidative stress on SARS-CoV and SARS-CoV-2 infections. We focused on the impact of antioxidants, like NADPH and glutathione, and redox proteins, such as thioredoxin and protein disulfide isomerase, that maintain the disulfide-thiol balance in the cell. The possible influence of these biomolecules on the binding of viral protein with the host cell angiotensin-converting enzyme II receptor protein as well as on the severity of COVID-19 infection was discussed.

The redox-dependent changes on the binding between the receptor-binding domain of the severe acute respiratory syndrome-coronavirus-2 spike protein and the peptidase domain of the human cell surface receptor angiotensinconverting enzyme II were investigated by performing molecular dynamics simulations. The reduced states of the protein partners were generated in silico by converting the disulfides to thiols. The role of redox transformation on the protein−protein binding affinity was assessed from the time-evolved structures after 200 ns simulations using electrostatic field calculations and implicit solvation. The present simulations revealed that the bending motion at the protein−protein interface is significantly altered when the disulfides are reduced to thiols. In the native complex, the presence of disulfide bonds preserves the structural complementarity of the protein partners and maintains the intrinsic conformational dynamics. Also, the study demonstrates that when already bound, the disulfide-to-thiol conversion of the receptorbinding domain has a limited impact on the binding of the spike protein to the receptor. However, if the reduction occurs before binding to the receptor, a spectacular conformational change of the receptor-binding domain occurs that fully impairs the binding. In other words, the formation of disulfide bonds, prevalent during oxidative stress, creates a conformation ready to bind to the receptor. Taken together, the present study demonstrates the role of pre-existing oxidative stress in elevating the binding affinity of the spike protein for the human receptor, offering future clues for alternate therapeutic possibilities.

Polyethylene glycol (PEG) is a polyether compound commonly used in biological research and medicine because it is biologically inert. This simple polymer exists in variable chain lengths (and molecular weights). As they are devoid of any contiguous π-system, PEGs are expected to lack fluorescence properties. However, recent studies suggested the occurrence of fluorescence properties in non-traditional fluorophores like PEGs. Herein, a thorough investigation has been conducted to explore if PEG 20k fluoresces. Results of this combined experimental and computational study suggested that although PEG 20k could exhibit "through-space" delocalization of lone pairs of electrons in aggregates/clusters, formed via intermolecular and intramolecular interactions, the actual contributor of fluorescence between 300 and 400 nm is the stabilizer molecule, i.e., 3-tert-butyl-4-hydroxyanisole present in the commercially available PEG 20k. Therefore, the reported fluorescence properties of PEG should be taken with a grain of salt, warranting further investigation.