CORONAVIRUS AND ITS MAIN PROTEASE: AN INSIGHT FOR DRUGS DESIGN BY MOLECULAR DOCKING

Many virus need their sulphydryl groups to be reduced in order to be allowed to enter cells. SARS-CoV-2, which belongs to Coronaviridae family and is responsible for coronavirus disease 2019 or COVID-19, has cysteine-rich proteins in its capsid as the main CoV protease (MPRO), which must be intact and active maintaining the viral activity. Considering that MPRO is an important molecular target for development of antiviral drugs, this work motivation was the structural study of the possible ways of interaction between drugs and viral cysteines by molecular docking technique for design of new potential inhibitors of MPRO and its virulence.

Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients

Summary Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Moreover, several recent reports showed a direct association between the onset of IAS and the consumption of dietary supplements containing alpha-lipoic acid (LA). Insulinoma remains the most prevalent cause of hypersulinaemic hypoglycaemia in Caucasians. Consequently, primary investigation in these patients is generally focused on localisation of the pancreatic tumour, often with invasive procedures followed by surgery. We described a case of an Italian woman presenting to us with severe recurrent hypoglycaemia associated with high insulin and C-peptide levels and no evidence of pancreatic lesions at imaging diagnostic procedures. She had taken LA until 2 weeks before hospitalisation. After an evaluation of her drug history, an autoimmune form of hypoglycaemia was suspected and the titre of insulin autoantibodies was found to be markedly elevated. This allowed us to diagnose LA-related IAS, thus preventing any unnecessary surgery and avoiding invasive diagnostic interventions. Learning points: IAS is a rare cause of hyperinsulinaemic hypoglycaemia that typically affects Asian population, but it has been increasingly recognised in Caucasian patients. It should be considered among the differential diagnosis of hyperinsulinaemic hypoglycaemia to avoid unnecessary diagnostic investigations and surgery. It should be suspected in the presence of very high serum insulin levels (100–10 000 μU/mL) associated with high C-peptide levels. There is a strong association with administration of drugs containing sulphydryl groups included LA, a dietary supplement commonly used in Western countries to treat peripheral neuropathy.

Evaluation of a Summary Score for Dyslipidemia, Oxidative Stress and Inflammation (The Doi Score) in Women with Polycystic Ovary Syndrome and its Relationship with Obesity

SummaryBackground:Polycystic ovary syndrome (PCOS) is a cardiometabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients.Methods:Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls.Results:PCOS patients had significantly higher oxy-score compared to controls (P<0.001). In addition, the DOI score was significantly higher in PCOS patients (P<0.001) as the dyslipidemia (P<0.05) and inflammatory scores (P<0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P<0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P<0.001).Conclusion:PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients.

Evaluation of a Summary Score for Dyslipidemia, Oxidative Stress and Inflammation (The Doi Score) in Women with Polycystic Ovary Syndrome and Its Relationship with Obesity

SummaryBackground: Polycystic ovary syndrome (PCOS) is a cardiometabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients. Methods: Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls. Results: PCOS patients had significantly higher oxy-score compared to controls (P<0.001). In addition, the DOI score was significantly higher in PCOS patients (P<0.001) as the dyslipidemia (P<0.05) and inflammatory scores (P<0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P<0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P<0.001). Conclusion: PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients.

Carbaryl and Human Health: A Review

Carbaryl (1-naphthalenylmethylcarbamate) is one of the most frequently used carbamate insecticides. Carbaryl has elicited some serious carcinogenic activity in the chronic rodent studies and has also been found to cause tumors in the liver. Though carbaryl is relatively safe to mammals, but carbaryl causes damage to hepatocytes. It has other biochemical effects, as it reacts with reduced glutathione and probably directly with other accessible protein hydroxyl and sulphydryl groups or indirectly through reactions involving the glutathione conjugate. In mammals, carbaryl inhibits acetylcholinesterase causing several neural problems. Some recent reports suggest it can bind human melatonin receptors exerting serious implications on human health. Here in this review an attempt has been made to summarise carbaryl’s mode of action and its ill effects on human health.

Biochemical Quality Indicators and Enzymatic Activity of Wheat Flour from the Aspect of Climatic Conditions

The contents of free sulphydryl groups (SH), disulphide bonds (SS), and free amino groups (NH2) were determined in order to estimate the extent of climatic condition influence on gluten quality. The analysis included four bread wheat varieties grown in two production years (2011 and 2012) with different climatic conditions in different locations. According to our previously reported results, the working hypothesis was that enzyme activity for breadmaking purpose was insufficient. The aim of this paper was to study the influence of naturally present enzymes on the bread quality by the addition of previously extracted and freeze-dried albumins to the base flour as an additive. The selection of samples was made on the basis of different combinations of proteolytic and α-amylolytic enzymes activity levels. For samples from 2012 production year, the content of SH groups was significantly higher. Regarding the SS content, the obtained results exhibited the opposite trend. Variations in NH2 content were dominantly caused by temperature treatment of tested samples. The addition of freeze-dried albumins to bread improved its specific volume in a lesser extent, while bread crumb texture was significantly improved.

Equilibrium Studies of the Reaction of Turkey (Meleagris gallopavo) Haemoglobin Sulphydryl Groups with 5,5′-dithiobis(2-nitrobenzoate): Tertiary Conformational Change in Turkey Haemoglobin Induced by Inositol hexakisphosphate

The red blood cell of turkey contains two haemoglobin types, major and minor components. In the present study, the equilibrium constant, Kequ, for the reaction of 5,5′-dithiobis(2-nitrobenzoate), DTNB, with the sulphydryl group of the major turkey aquomethaemoglobin was determined at 25°C as a function of pH. Kequ varies by about 2 to 3 orders of magnitude between pH 5.6 and 9.0 for both haemoglobin [stripped and in the presence of inositol hexakisphosphate (inositol-P6)]. Calculations from the pH dependence of Kequ showed that in the r ⇌ t tertiary conformational transition of aquomethae-moglobin, the t isomer population was 0.26 %. In the presence of inositol-P6, the t isomer population increased to 9.08 %. The results showed that while inositol-P6 increased the relative population of the t tertiary conformation by changing the relative distribution of two protein conformations, it had no effect on Kequ. The effect of Inositol-P6 on the nature and number of groups linked to the DTNB reaction was also determined.