Background:: COVID-19 has spread rapidly in many countries of the world and poses a serious threat to global public health, yet no specific drug has been identified or currently available for its treatment. Since it may take years to design a drug for treatment, the shortest and most effective way now is to screen the available drugs or active substances by molecular docking methods. Objective:: The aim of this study is to investigate the potential for use in COVID-19 treatment by investigating the inhibitory effects of Glycyrrhiza glabra main active ingredients on COVID-19 main protease (SARS-CoV-2,), SARS-CoV-2 - ACE2 Complex and ACE-2 by molecular docking method, which are known to have antiviral effects on SARS-CoV. Material and Methods:: Molecular docking was performed by use of Autodock 4.2 to analyse the probability of docking. Several compounds that extracted from the root of the licorice plant (glycyrrhizic acid, glabridin, 6-azauridine, pyrazofurin and mycophenolic acid) was docked COVID-19 Mpro and docking results were analysed by Autodock 4.2 and Biovia Discovery Studio Visualizer 2020. The evaluation was based on the docking score (binding energies) calculated by Autodock 4.2. Nelfinavir was used as standards for comparison. Results:: As a result of the study, the compounds of Glabridin in COVID-19 main protease (6LU7), ACE-2 (1R4L) and SARS-CoV-2, - ACE2 Complex (6LZG) have very low binding energy (-8.75 to -7.64) and low potential to inhibition constant has been found to have. Conclusion:: These results suggests that Glabridin appeared to have the best potential to act as a COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.
Objective: This study aimed to investigate the inhibitory effects of sedative, analgesic and anaesthetic drugs on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin converting enzyme-2 (ACE-2) and SARS-CoV-2-ACE-2 complex through molecular docking and their potential use for the treatment of coronavirus disease-2019 (COVID-19). Materials and Methods: In this study, molecular docking was employed to investigate the molecular interaction between drugs under clinical tests (chloroquine, hydroxychloroquine and nelfinavir) and the most commonly used drugs for sedation, analgesia and anaesthesia, such as inhibitors (desflurane, dexmedetomidine, fentanyl, ketamine, midazolam, propofol, remifentanil and sevoflurane) of three different enzymes (6LU7, 1R4L and 6LZG). Autodock 4.2 Lamarckian Genetic Algorithm was used to analyse the probability of the molecular docking. The evaluation was based on docking points calculated by Biovia Discovery Studio Visualizer 2020. As a result of the molecular docking, interaction types, such as hydrogen-electrostatic and van der Waals between enzymes and drugs, were determined and the results were compared. Results: Among the drugs included in the study, fentanyl had a low binding energy (-8.75 to -7.64 kcal/mol) for SARS-CoV-2, ACE-2 and SARS-CoV-2-ACE-2 complex and can inhibit these proteins at low concentrations. Apart from fentanyl, midazolam, ketamine, propofol and remifentanil can also inhibit proteins; however, sevoflurane and desflurane were found to be ineffective. Conclusion: Our findings suggest that fentanyl is preferable for sedation, analgesia and anaesthesia in COVID-19 patients and that total intravenous anaesthesia can be preferred for general anaesthesia. However, experimental and clinical studies are required to determine the efficacy of these substances in treatment.
Background: Lipoid proteinosis (LP) is an autosomal recessive transfer lysosomal storage disease, characterised by the accumulation of hyalin substance in the mucous membranes, skin, internal organs and brain, for which there is no biochemical diagnostic method. Objective: The aim of this study was to determine the carnitine and acylcarnitine metabolic profile with LC-MS/MS in LP patients and thereby examine the potential of this as a new biochemical method in the determination of biochemical markers in LP patients. Methods: In this study, 27 carnitine and acylcarnitine esters were measured with LC-MS/MS in serum samples taken from 14 healthy control subjects and 14 patients who presented at the Skin and Venereal Diseases Polyclinic and were diagnosed with LP as a result of clinical, radiological and histopathological examinations. Results: The results of the study showed that C0 (free carnitine) C3, C4, C4:DC, C5DC, C6, C8, C14:1, C14:2, C16 and C18 acylcarnitines were statistically significantly reduced in the LP patients (p<0.05, p<0.01). Conclusion: It was concluded that the application of carnitine profile screening, which is an inexpensive, rapid and reliable method, could make a contribution to the differential diagnosis as aa supporting laboratory test in individuals with suspected LP.
Background: The blood level of tacrolimus (TAC) used for post-transplant immunosuppression should be within the therapeutic index. Geriatric individuals may be at risk of organ rejection because in this age group, routine drug use is usually disrupted and the bioavailability of aging-related drugs is decreased. Objective: The aim of this study was to analyze the age-related variability of blood TAC levels in patients in Turkey. Methods: In this study, 697,616 patients who underwent TAC measurement in the laboratories of public, private, and university hospitals between 2018 and 2020 were identified from the Health-net database of the Ministry of Health. The results of patients aged ≥65 years were compared with those of patients aged <65 years. The differences between the sexes in the same age group were also examined. Data from the Turkish Ministry of Health National Electronic Database were used to design a multicenter retrospective cohort study. Results: The study included 697,616 patients. The mean TAC concentration was 7.2 ± 6.25 ng/mL for all the patients, 7.13 ± 6.7 ng/mL for the female patients, and 7.24 ± 5.96 ng/mL for the male patients. A statistically significant difference in TAC concentration was found between the men and women in the general population. Groups aged ≥65 years were compared among themselves. A statistically significant decrease in TAC concentration was found only in the age group of 75–79 years (5.63 ± 4.09 ng/mL) of women compared with the men. In all other age groups, the TAC levels of the men were lower. Conclusions: The proportion of patients with TAC concentrations lower than the therapeutic index was higher in the groups aged ≥65 years. Thus, patients aged ≥65 years may be at risk of organ rejection, as optimum immunosuppression cannot be achieved. In these patients, more frequent drug monitoring and providing training to ensure the compliance of the patient and the patient's relatives in the use of TAC may be recommended.
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