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.

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 impacts on enzyme function. However, few studies have investigated the role of distal residues on enzymatic catalysis. In the present study, 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.

Differences in the structural and thermodynamic properties of enzymes adapted to different temperatures indicate that broad range temperature active enzymes can be designed by incorporating cold activity in thermophilic enzymes....

Naltrexone (NTX) is a nonspecific opioid antagonist that binds to mu‐, kappa‐, and delta‐opioid receptors. Previous research has demonstrated that rats given chronic, intermittent sucrose access have increased endorphin function. We have shown that rats given chronic, intermittent sucrose can discriminate 1.0 mg/kg NTX from saline in a two‐lever, operant choice procedure. We wondered if NTX's discriminative stimulus effects were mediated by kappa‐opioid receptors. To examine this possibility, we tested the effects of the kappa‐opioid agonist U69,593 in our discrimination procedure. Male Sprague‐Dawley rats were given access to 12‐hour access to a 25% sucrose solution and trained to discriminate NTX (1.0 mg/kg) from saline. Once discrimination criteria (80% or greater condition‐appropriate responding for 8 of 10 consecutive sessions) were reached, generalization testing began. We used a cumulative dosing procedure to determine if U69,593 alters the ability of NTX to produce its discriminative stimulus effects. Subjects were pretreated with U69,593 (0.0001 mg/kg – 0.1 mg/kg, s.c.) followed by increasing doses of NTX (0.001 mg.kg – 10.0 mg/kg, s.c.). Fifteen to 30 minutes after the injection, a test session began. Injections continued until response rates were suppressed or 10.0 mg/kg NTX was administered. Reversal tests were also conducted. During these tests, the training dose of NTX was administered and a test session began 15 minutes later. Then a single dose of U69,593 (0.001 mg/kg – 0.1 mg/kg, s.c.) was administered, followed by test sessions 15 to 120 minutes after the injection. U69,593 did not significantly alter the discriminative stimulus effects of NTX. This suggests that kappa‐opioid receptor antagonism is not sufficient to produce NTX's discriminative stimulus effects in rats given chronic, intermittent sucrose access.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Drug discrimination has been a useful behavioral approach for understanding the neuropharmacological mechanisms of drug‐induced stimuli. Naltrexone (NTX) is an opioid antagonist with known binding affinities for mu‐, kappa‐, and delta‐opioid receptors. Our present study investigates the receptor‐mediated discriminative stimulus effects of NTX, as well as differences in stimulus control maintenance. We previously reported that rats given chronic, intermittent sucrose access can be trained to discriminate NTX (0.1 – 3.2 mg/kg) from saline (SAL). In the present study, nine male Sprague‐Dawley rats were housed in a 12‐hour light, 12‐hour dark cycle. During the dark cycle, subjects were given access to 25% sucrose solution and were trained to discriminate NTX from SAL. Discrimination criteria were defined as 80% or greater condition‐appropriate responding before the first reinforcer delivery and total session for 8 out of 10 consecutive sessions. After these criteria were met, generalization testing was conducted. Generalization tests included an injection of SAL followed by a dose of NTX differing from the training dose. Between test sessions, subjects followed a single alternation training procedure to ensure maintenance of NTX/SAL discrimination. Our single alternation procedure required two consecutive sessions of criteria‐appropriate responding. We observed variations in accuracy during training sessions conducted after acquisition criteria were completed. During post‐acquisition training sessions, subjects averaged 82.05% condition‐appropriate responding when given SAL and averaged 68.15% when given NTX. Means were significantly different from each other and chance performance. SAL‐appropriate responding was not significantly different from our criteria of 80%, while NTX‐appropriate responding did differ. Rapid improvement in NTX‐appropriate accuracy was observed leading up to discrimination acquisition. Stimulus control was maintained for an average of 25 sessions before accuracy of NTX‐appropriate responding began to decrease. In some subjects, accuracy of SAL‐appropriate responding was maintained while accuracy of NTX‐appropriate responding fluctuated over time. The inverse was true for other subjects. A third subset of subjects showed varying accuracy in response to both conditions. Rate suppression occurred in several subjects following NTX administration and was attenuated by reducing the NTX dose. Doses as small as 0.0001 mg/kg NTX generalized to the training dose in some subjects, indicating sensitivity development. A single dose of the kappa‐opioid agonist U69,593 (0.01 mg/kg – 0.1 mg/kg, s.c.) was administered 30 minutes prior to NTX (0.0001 mg/kg – 1.0 mg/kg, s.c.). U69,593 eliminated NTX‐appropriate responding in some, but not all, subjects. Our data show that while NTX has the ability to produce discriminative stimulus effects in rats given chronic, intermittent sucrose access, there are individual differences in post‐acquisition stimulus control. Support or Funding Information UW‐EC ORSP Grant