ABSTRACT
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.
Subject(s)
COVID-19/metabolism , Oxidative Stress , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/metabolism , Severe acute respiratory syndrome-related coronavirus/physiology , Acetylcysteine/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/pharmacology , Drug Discovery , Humans , Models, Molecular , Oxidative Stress/drug effects , SARS-CoV-2/drug effects , Severe Acute Respiratory Syndrome/drug therapy , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/metabolism , COVID-19 Drug TreatmentABSTRACT
Enzymes play important roles in many biological processes. Amino acid residues in the active site pocket of an enzyme, which are in direct contact with the substrate(s), are generally believed to be critical for substrate recognition and catalysis. Identifying and understanding how these "catalytic" residues help enzymes achieve enormous rate enhancement has been the focus of many structural and biochemical studies over the past several decades. Recent studies have shown that enzymes are intrinsically dynamic and dynamic coupling between distant structural elements is essential for effective catalysis in modular enzymes. Therefore, distal residues are expected to have impact on enzyme function. However, few studies have investigated the role of distal residues on enzymatic catalysis. In the present study, the effects of distal residue mutations on the catalytic function of an aminoacyl-tRNA synthetase, namely, prolyl-tRNA synthase, were investigated. The present study demonstrates that distal residues significantly contribute to catalysis of the modular Escherichia coli prolyl-tRNA synthetase by maintaining intrinsic protein flexibility.
