Could boron compounds be effective against SARS-CoV-2?

BACKGROUND: Seven dioxaborole compounds are investigated in this study. Structural and spectral characterization is done at M062X/6-31+G(d,p) level in the water. Active sites of these compounds are determined using molecular electrostatic potential (MEP) maps. Electrophilic and nucleophilic attack regions are determined. AIM: We aimed to determine whether Boron-Containing Compounds (BCCs) inhibitor used in the treatment of COVID-19 are effective against SARS Cov-2 in silico. RESULTS AND CONCLUSION: Since SARS-CoV-2 is a worldwide health problem, anti-viral properties of studied boron-containing compounds were investigated by molecular docking calculations. In addition to these calculations, MM/PSBA calculations were performed. It was found that boron compounds can be good drug candidate against SARS-CoV-2 and the best compound is ((R)-1-((S)-3-(4-(aminomethyl)phenyl)-2-benzamidopropanamido)-4-guanidinobutyl)boronic acid (C26) (Tab. 2, Fig. 6, Ref. 29). Text in PDF www.elis.sk Keywords: boronate ester, dioxaborole, in silico, SARS-CoV-2, MD calculations.

Could Peganum harmala be effective in the treatment of COVID-19?

BACKGROUND: Predominant molecules in Peganum harmala leaves were detected using gas chromatography-mass spectrometry (GC-MS). Based on the results of this analysis, most alkaloids, flavonoids and triterpenoids in found P. harmala was compiled from the literature in order to develop and lead the production of effective inhibitor drugs for ACE2, main protease, and RNA dependent RNA polymerase (RdRp) proteins of SARS-CoV-2 virus, which is today's most contagious and deadly disease. AIM: By comparing FDA-approved drugs used in the treatment of COVID-19, we aimed to determine whether the molecules in P. harmala are effective against SARS CoV-2 in silico. RESULTS AND CONCLUSION: P. harmala molecules were selected as drug candidates from the PubChem web tool. Afterwards, molecular docking calculations of these inhibitor molecules were made with Maestro Molecular modeling program by Schrödinger. The comparison of molecules with high inhibitory activities with FDA-approved drugs was made. With molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations, docking calculations of molecules that have high inhibitory activity, were tried to be verified by calculations in the range of 0-100 nanoseconds (Tab. 4, Fig. 6, Ref. 53).

Determination of inhibitor activity of drugs against the COVID-19.

BACKGROUND: It is the SARS-CoV-2 virus, one of the most significant diseases of today's world. Due to the high transmission of this disease, studies are ongoing to discover an inhibitor drug that can stop this disease. In this study, inhibitory drugs used for many diseases were tried to stop the SARS-CoV-2 virus. AIM: In the calculations made, inhibitor molecules for the SARS-CoV-2 virus were calculated by molecular docking method. RESULTS AND CONCLUSION: Inhibitory activities of SARS-CoV-2 virus against spike glycoprotein (PDB ID: 6M0J, 6LZG), main protease (PDB ID: 5RGG, 6WTT), and RNA dependent RNA polymerase (RdRp) (PDB ID: 6YYT, 7BV2) proteins were compared. Then, docking calculations were supported by calculations by MM-PSBA of the inhibitor with the highest activity. Afterwards, it was compared with FDA approved drugs for the SARS-CoV-2 virus. It was found that the Carvedilol molecule was the best against RNA dependent RNA polymerase (RdRp) protein of SARS-CoV-2 (Tab. 4, Fig. 9, Ref. 42).

Could boron-containing compounds (BCCs) be effective against SARS-CoV-2 as anti-viral agent?

BACKGROUND: Seven dioxaborole compounds are investigated in this study. Structural and spectral characterizations are done at the M062X/6-31+G(d,p) level in water. Active sites of these compounds are determined by contour plots of frontier molecular orbital and molecular electrostatic potential (MEP) maps. Electrophilic and nucleophilic attack regions are determined. Since SARS-CoV-2 is a worldwide health problem, antiviral properties of studied boron-containing compounds are investigated by molecular docking calculations. In addition to these calculations, MM/PSBA calculations are performed. RESULTS AND CONCLUSION: It is found that the studied boron compounds can be good drug candidates against the main protease of SARS-CoV-2, while the best of them is 4,6-di-tert-butyl-2-(4-methoxyphenyl)benzo[d][1,3,2] dioxaborole (B2) (Tab. 3, Fig. 8, Ref. 23).

Are clarithromycin, azithromycin and their analogues effective in the treatment of COVID19?

BACKGROUND: SARS-CoV-2, which started in Wuhan and later affected the whole world, is the most important disease of the world today. Many ways to inhibit SARS-CoV-2 virus are sought to prevent the spread of this virus. Azithromycin and clarithromycin are considered for the treatment of the SARS-CoV-2 virus, which has a high similarity to previous colonic diseases. AIM: We aimed to determine whether azithromycin and clarithromycin, the RNA-dependent RNA polymerase protein inhibitor used in the treatment of COVID-19, is effective against SARS Cov-2 in silico. RESULTS AND CONCLUSION: The 503 analogues of azithromycin and clarithromycin were studied to target SARS-CoV-2 the RNA-dependent RNA polymerase protein inhibition. Maestro program was used to compare the inhibition activities of these analogues. A detailed comparison was made using the numerical value of many parameters obtained. ADME / T properties were then examined to determine the effects and reactions of analogues on human metabolism. In this study, the SARS-CoV2 virus is 6NUR and 6NUS, which is the RNA-dependent RNA polymerase protein. Among these proteins, the best inhibitor among the 503 analogues according to the docking score parameter was 9851445 with a great difference. This analogue was an analogue of azithromycin (Tab. 3, Fig. 6, Ref. 58).

How do arbidol and its analogs inhibit the SARS-CoV-2?

BACKGROUND: COVID-19 is not fully known and causes severe inflammation and cytokine storm. It has many symptoms, such as: fever, sore throat, headache, dyspnoea, and diarrhoea. Arbidol was used in the treatment of COVID19, which was the most critical health problem in the world. However, the desired recovery was not achieved with Arbidol. Many countries still use this drug in the treatment of COVID19. AIM: We aimed to determine whether Arbidol, the hemagglutinin esterase inhibitor used in the treatment of COVID-19, was effective against SARS Cov-2 in silico. RESULTS AND CONCLUSION: The similarity between hemagglutinin and spike proteins were reported due to the fact that inhibition properties of Arbidol and its 39 analogues were examined in detail against hemagglutinin esterase and spike glycoproteins. CID 1070884 and CID 1207786 were found to be more active against hemagglutinin esterase than in Arbidol, while these compounds were inactive against spike glycoproteins. The interaction mechanism was clarified between arbidol and spike proteins. Phenylalanine, tyrosine, glycine, lysine, and aspartic acid were found to be the headliner amino acids in the interactions between Arbidol and binding domains of spike glycoproteins in the SARS-CoV2 (Tab. 3, Fig. 8, Ref. 28).

Prevalence of sicca symptoms and Sjögren's syndrome in coeliac patients and healthy controls.

Objective: There has been no previous study comparing the frequency of sicca symptoms and Sjögren's syndrome (SS) in coeliac patients (CPs) and healthy controls (HCs) using a tight screening method. The aim of this study was to compare the frequency of sicca symptoms and SS in HCs and CPs.Method: The study included 80 CPs and 100 HCs. This study was designed as a case-control study with four phases. The frequency of SS in CPs and HCs was defined according to the 2002 American-European Consensus Group (AECG) and 2012 American College of Rheumatology (ACR) classification criteria. The frequency of sicca symptoms and SS was compared between CPs and HCs.Results: Ocular and oral symptoms occurred in 22% and 26% of CPs, respectively, compared to 13% and 10% of HCs, respectively. Proportions with oral symptoms were statistically significantly different between CPs and HCs (p = 0.005), whereas there was no significant difference for ocular symptoms (p = 0.113). According to ACR and AECG criteria, the prevalence of SS was 3.8% and 5.0% in CPs and 3.0% and 2.0% in HCs, respectively.Conclusion: Although oral symptoms were more frequent in CPs than in HCs, the frequency of SS was not different between the groups. The increased frequency of oral symptoms may be related to reasons other than autoimmunity.

Assesment life quality of familial Mediterranean fever patients by short form-36 and its relationship with disease parameters.

BACKGROUND: Familial Mediterranean fever is an auto-inflammatory disorder. Long term complications of the disease include decreased quality of life. The measurement of quality of life in the patients with chronic disease has become an important research topic during the last years. AIM: We aimed to evaluate life quality of the FMF patients by SF-36, and examine its relationship with the disease parameters. PATIENTS AND METHODS: One hundred voluntary patients (69 female, 31 male) admitted to the rheumatology clinic were included in the study. The control group consisted of 100 healthy individuals. All subjects in the study were asked to complete SF-36 questionnaire. Age of onset of FMF, age at diagnosis, age at the beginning of colchicine therapy, number of attacks per month, family history of FMF and dialysis were inquired of patients with FMF. Disease severity was determined using the FMF severity score. RESULTS: The mean age of the patient group was 31±12 and that of the control group was 29±9. Sixty-nine patients (69%) were female, and 31 patients were male (31%) in both groups. The mean scores of the physical function, physical role function, emotional role function, mental health, and general health parameters of the patients were statistically significantly lower than those of healthy volunteers (p < 0.05). The difference in social function and vitality between two groups was found to be insignificant (p > 0.05). CONCLUSIONS: We have shown that FMF had a negative impact on SF-36. FMF reduces quality of life both in physical and mental dimensions.

Steatohepatitis and liver cirrhosis in Chanarin-Dorfman syndrome with a new ABDH5 mutation.

Chanarin-Dorfman syndrome (CDS) is an autosomal recessive neutral lipid storage disease. It is very rare and characterized by ichtiosis, intracellular fat droplets in leucocytes (Jordan anomaly) and involvement of multiple tissues (skeletal muscle, central nervous system, bone marrow, eye and ear) mainly the liver. Our patients were diagnosed as CDS because they had ichtiosis, Jordon anomaly of leucocytes in peripheral blood smear, liver involvement and presence of homozygous 88 insertion C frame shift mutation on exon 4 of ABHD5/CGI-58 gene in genetic analysis. Our cases were two sisters. One of them developed severe steatohepatitis on age 19 and the other one was diagnosed as decompensated cirrhosis when she was 26 years old. We report here a new mutation in comparative gene identification-58 (CGI-58) gene causing syndactyly and steatohepatitis induced early cirrhosis.

Heterotopic gastric mucosa (inlet patch): endoscopic prevalence, histopathological, demographical and clinical characteristics.

OBJECTIVE: Heterotopic gastric mucosa (HGM) is found in the cervical oesophagus, just below the upper oesophageal sphincter, and has generally been overlooked by endoscopists. The objective of the present study is to determine endoscopic prevalence and histopathological and clinical characteristics of HGM and to classify patients according to their clinicopathological features. METHOD: A total of 911 consecutive patients (436 M and 475 F) who were admitted to our Endoscopy Unit were examined. HGM type and the presence of Helicobacter pylori (Hp) either in the stomach or in the HGM were histopathologically evaluated. RESULTS: Of the 911 patients, 33 (25 M and 8 F) were found to have HGM. HGM prevalence was determined to be 3.6%. On the basis of HGM patients' symptoms, only dysphagia was significantly correlated with the size of HGM (p < 0.05). Hp was positive in 29.2% of HGM. Clinicopathological classification of the patients showed that 20 patients were HGM type 1 and 13 were HGM type 2. None of the patients had HGM type 3, 4 or 5. CONCLUSION: Prevalence of HGM was 3.6%. Dysphagia was found related with the size of HGM. This may be associated with larger HGMs' causing more acid secretion.

Churg-Strauss syndrome associated with acalculous cholecystitis and liver involvement.

We describe a 65-year-old man who had liver involvement with Churg-Strauss syndrome. He was admitted to the hospital because of fever, weight loss, dyspnea, abdominal pain, skin lesions and paraesthesias. His past medical history revealed a diagnosis of acalculous cholecystitis that had been made eight months earlier. Microscopic examination of a gall bladder biopsy specimen obtained at that time revealed an increase in extravascular eosinophils. There was evidence of a new bilateral pulmonary disease with bronchoconstriction and a transient infiltrated lesion in the right upper lung. The patient's white cell count was 14 620 per cubic millimetre, with 39% eosinophils (5800 per cubic millimetre) and 39% neutrophils. IgE was 503 g/L (normal range, 0 to 100 g/L). Liver function tests were mildly elevated. Fine needle liver biopsy showed active interface hepatitis. A diagnosis of Churg-Strauss syndrome was made. In this patient the syndrome occurred in a rare association with hepatitis, likely due to immunologic events in the liver. The patient was successfully treated with 60 mg/day of prednisolone monotherapy.

The value of ultrasonography and computerized tomography in estimating the histopathological severity of nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Liver biopsy is the gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but is an invasive method. There is a need for non-invasive methods that can reflect the histopathological severity of NASH. The aim of this study was to compare the ultrasonography and computerized tomography findings with the histopathological severity in patients with NASH. MATERIAL AND METHODS: Twenty-two consecutive patients with biopsy proven NASH and 20 age- and sex-matched healthy individuals were enrolled. Clinical and demographic data were collected at the time of liver biopsy. Histopathological grading and staging were made by an expert pathologist. Each patient underwent ultrasonography and computerized tomography. RESULTS: Liver ultrasonographic findings were not correlated with histopathological grade and stage (r: 0.134, P > 0.05; r: 0.130, P > 0.05). Mean liver densities obtained by computed tomography of NASH patients were lower than that of controls (P < 0.05) and liver/spleen density ratios were lower than that of controls (P < 0.05). These results were significantly correlated with histopathological grade (r: -0.716, P < 0.001; r: -0.663, P: 0.001), but not with the histopathologic stage (r: -0.416, P: 0.05; r: -0.356, P: 0.1). CONCLUSIONS: Ultrasonography findings do not reflect histopathological severity in patients with NASH. Computed tomography attenuation of the liver is significantly correlated with histopathologic grade but not with histopathological stage.

Levels of serum vitamin A, alpha-tocopherol and malondialdehyde in patients with non-alcoholic steatohepatitis: relationship with histopathologic severity.

The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum levels of vitamin A and alpha-tocopherol as antioxidants and determine relationship of these with histopathologic severity in patients with non-alcoholic steatohepatitis (NASH). Twenty-nine patients with biopsy-proven NASH were included to study. NASH were histopathologically scored for grading and staging. Serum MDA and vitamin A levels were increased in patients with NASH and simple steatosis as compared to healthy control group. Serum alpha-tocopherol levels measured in simple steatosis and NASH were significantly lower than in healthy control group. There was no significant difference between grade/stage 0-1 and grade/stage 2-3 in terms of MDA, vitamin A and alpha-tocopherol levels. Serum MDA and vitamin A levels are increased in simple steatosis and NASH. MDA, vitamin A and alpha-tocopherol levels in NASH were not associated with the histopathologic severity.