A target site for template-based design of measles virus entry inhibitors

Measles virus (MV) constitutes a principal cause of worldwide mortality, accounting for almost 1 million deaths annually. Although a live-attenuated vaccine protects against MV, vaccination efficiency of young infants is low because of interference by maternal antibodies. Parental concerns about vaccination safety further contribute to waning herd immunity in developed countries, resulting in recent MV outbreaks. The development of novel antivirals that close the vaccination gap in infants and silence viral outbreaks is thus highly desirable. We previously identified a microdomain in the MV fusion protein (F protein) that is structurally conserved in the paramyxovirus family and constitutes a promising target site for rationally designed antivirals. Here we report the template-based development of a small-molecule MV inhibitor, providing proof-of-concept for our approach. This lead compound specifically inhibits fusion and spread of live MV and MV glycoprotein-induced membrane fusion. The inhibitor induces negligible cytotoxicity and does not interfere with receptor binding or F protein biosynthesis or transport but prevents F protein-induced lipid mixing. Mutations in the postulated target site alter viral sensitivity to inhibition. In silico docking of the compound in this microdomain suggests a binding model that is experimentally corroborated by a structure-activity analysis of the compound and the inhibition profile of mutated F proteins. A second-generation compound designed on the basis of the interaction model shows a 200-fold increase in antiviral activity, creating the basis for novel MV therapeutics. This template-based design approach for MV may be applicable to other clinically relevant members of the paramyxovirus family.     

A novel mutation of sgk-1 gene in central serous chorioretinopathy

AIM

To investigate the association of serum glucocorticoid kinase gene-1 (SGK-1) DNA variants with chronic central serous chorioretinopathy (CSC).

METHODS

We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction (PCR) amplification. SGK1 gene was sequenced by using BigDye^® Terminator v3.1 cycle sequencing KIT (Applied Biosystems, Foster City, CA, USA). The SGK1 gene and its variants were investigated in CSC patient group and control group.

RESULTS

We identified a new polymorphism M32V in two person in the patient group (Minor allele frequency (MAF)=0.009) on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK 1 gene but not associated with CSC (P=0.68). An intrinsic rs1743966 is also not associated (P=0.28).

CONCLUSIONS

The new polymorphism M32V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.     

Association of interleukin (IL)-4 gene intron 3 VNTR polymorphism with multiple sclerosis in Turkish population

Objective

Genetic risk factors are known to contribute to the etiology of multiple sclerosis (MS). Interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases. The aim of this study was to explore the frequency of IL-4 gene intron 3 VNTR (variable number tandem repeat) polymorphism in a cohort of Turkish patients with MS.

Methods

The study included 125 patients with MS and 160 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the IL-4 gene intron 3 VNTR polymorphism.

Results

The distribution of genotype and allele frequencies of IL-4 gene intron 3 VNTR polymorphism was statistically different between MS patients and control group (p = 0.003 and p = 0.002, respectively). There were no statistically significant association between IL-4 VNTR polymorphism and clinical and demographical characteristics of MS patients.

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism of the IL-4 gene was positively associated with predisposition to develop MS in Turkish population.     

Simple concentration method enables the use of gargle and mouthwash instead of nasopharyngeal swab sampling for the diagnosis of COVID-19 by PCR

European Journal of Clinical Microbiology & Infectious Diseases - Since its emergence in December 2019, SARS-CoV-2 is causing one of the most devastating pandemics in human history. Currently,...     

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.     

Dental radiographic procedures during COVID-19 outbreak and normalization period: recommendations on infection control

Oral Radiology - Dental professionals have always been meticulous about infection control due to high risk of cross-contamination during dental procedures. Nevertheless, there is an urgent need to...     

Evaluation of indirect microparticle activity and parameters of thrombin generation test in healthy infants

Introduction

Circulating microparticles support thrombin generation. The aim of this study is to determine the indirect microparticle activity and the parameters of thrombin generation in healthy infants.

Materials and methods

A total of 85 infants who were brought to follow-up visits were taken into the study. Blood samples were collected. Thrombin generation parameters and indirect microparticle activity were measured.

Results

The infants were divided into four groups according to the time of follow-up visits. Mean ages were 1.18 ± 0.19 months in Group 1, 6.15 ± 0.16 months in Group 2, 12.38 ± 0.46 months in Group 3 and 24.53 ± 0.39 months in Group 4, respectively. There was no statistical difference among the age-based groups with respect to the indirect microparticle activity. The lag time and the TTP levels in Group 1 were lower than that found in Group 2. The ETP and peak levels were higher in Group 1 than that of Group 2. The ETP and peak levels in Group 2 were found lower than those found in older children, but the TTP level was found relatively higher. Statistically correlations were found between indirect microparticle activity and all parameters of thrombin generation.

Conclusions

The absence of a difference in terms of age-based microparticle levels may suggest that the features of microparticles in healthy children of this age group are similar. Age-dependent changes in thrombin generation parameters may suggest a regulation mechanism for the thrombin generation system over the first years of life. The results may provide mean values for indirect microparticle activity and thrombin generation in this healthy group.     

Oral complaints of denture-wearing elderly people living in two nursing homes in istanbul, Turkey

Aim: The aim of this study was to observe and determine oral complaints of people aged 55 years or older, living in two nursing homes in Istanbul, Turkey, and their satisfaction with their complete or partial dentures by means of a simple questionnaire. Methods: Two old peoplea??s homes (one public and one private) in the district of Uskudar in Istanbul agreed to take part in this study. All residents who were available were invited to answer a piloted nine-point questionnaire with questions on age, gender, physical problems, eating, and communication, aesthetic denture wearing and psychological problems. The questions were asked in person by one investigator. The resulting data were entered into SPSS version 15. Results: Out of a total of 210 residents, 130 (61.9%) took part in the study, of whom 53% (n=71) of residents were living in the private nursing home and 60% (n=81) were female. One hundred and five (80%) were denture wearers. More than half of the residents (59%, n=79) were over 75 years old. Problems were mostly seen in older ages, especially those over 75 years old, over 60% of whom reported problems for all the variables listed in the questionnaire. Women were more aware of halitosis than men. Conclusions: The results of this study confirm those of previous studies and suggest that elderly people with dentures, and particularly complete dentures, frequently complain of a wide range of problems including: eating, social interaction and communication and these problems have a detrimental influence on their quality of life.