Computational screening of known broad-spectrum antiviral small organic molecules for potential influenza HA stem inhibitors.

With the emergence of new influenza virus strains that are resistant to current inhibitors such as oseltamivir (anti-neuraminidase (NA)) and amantadine (anti-M2 proton channel), influenza A viruses continue to be a serious threat to the public health worldwide. With this in view, there is a persistent need for the development of broader and more effective vaccines and therapeutics. Identification of broadly neutralizing antibodies (bNAbs) that recognize relatively invariant structures ‎on influenza haemagglutinin (HA) stem has invigorated efforts to develop universal influenza vaccines. The current computational study is designed to identify potential flavonoid inhibitors that bind to the contact epitopes of HA stem that are targeted by broadly neutralizing antibodies (bNAb). In this study, we utilized the three-dimensional crystallographic structure of different HA subtypes (H1, H2, H5, H3, and H7) in complex with bNAb to screen for potential broadly reactive influenza inhibitors. We performed Quantitative Structure-Activity and Relationship (QSAR) for 100 natural compounds known for their antiviral activity and performed molecular docking using AutoDock 4.2 suite. Furthermore, we conducted virtual screening of 1413 bioassay hit compounds by using virtual lab bench CLC Drug Discovery. The results showed 18 lead flavonoids with strong binding abilities to bNAb epitopes of various HA subtypes. These 18 broadly reactive compounds exhibited significant interactions with an average of seven Hbonds, docking energy of -22.43 kcal·mol-1, and minimum interaction ‎ energy of -4.65 kcal·mol-1, with functional contact residues. Procyanidin depicted strong interactions with group 1 HAs, whereas both sorbitol and procyanidin exhibited significant interactions with group 2 HAs. Using in silico docking analysis, we identified 18 bioactive flavonoids with potential strong binding cababilities to influenza HA-stems of various subtypes, which are the target for bNAb. The virtual screened bioassay hit compounds depicted a high number of Hbonds but low interaction and docking values compared to antiviral flavonoids. Using structure-based design and nanotechnology-based approaches, identified molecules could be modified to generate next generation anti-influenza drugs

The Implementation of an Integrated Management System at Qatar Biobank

Qatar Biobank (QBB) is a platform that will make vital health research possible through its collection of samples and information on health and lifestyle from the local population of Qatar. The goal of QBB is to collect, process, store, and finally share high-quality biological samples and associated data for research purposes with the research community. To do this, a series of standardized procedures following evidence-based practices are required, and QBB is achieving this by implementing an integrated management system (IMS) that incorporates ISO 9001: 2015 and ISO 27001: 2013 standards. ISO 9001 is one of the most commonly implemented quality management systems as it is applicable to any size of organization. ISO 27001: 2013 is increasingly popular as organizations look to manage their data and information security, especially in the light of the recent General Data Protection Regulation legislation and an ever-changing digital landscape. QBB has achieved certification in both ISO 9001: 2015 (originally 2008 standard) and ISO 27001: 2013 since 2014. In 2016, during preparations for recertification of both standards in 2017, QBB chose to integrate both of the management systems in preference to running them in parallel, without compromising the goals and objectives of QBB. The IMS has ensured that rigorous processes and controls are implemented to not only manage the quality of internal and external processes and services provided, but the privacy and confidentiality of data collected during a participant visit are consistently protected as well as a proactive approach to identifying and managing risk within the organization. This article will explore the impact of implementing an IMS on the continuous improvement of services within QBB

Molecular epidemiology of Rotavirus in children with gastroenteritis in Qatar

Acute gastroenteritis remains a major cause of morbidity and mortality of young children worldwide. The vast majority of diarrhea cases in developing and developed countries are attributable to the viruses and to a lesser extent to bacteria, fungi and toxins. Rotavirus (RV) is recognized as the most important etiological agent leading to acute gastroenteritis globally. In order to determine the burden and characteristics of RV infections in children in Qatar, profiling of circulating genotypes and their correlation with demographics and clinical manifestations were evaluated

Impact of Physical Exercise on Gut Microbiome, Inflammation, and the Pathobiology of Metabolic Disorders.

The gastrointestinal tract (GIT) harbors a complex and diverse microbial composition that outnumbers our own body cells and their gene contents. These microbes play a significant role in host metabolism and energy homeostasis. Emerging evidence suggests that the GIT microbiome significantly contributes to host health and that impairments in the microbiome may cause the development of metabolic diseases. The microbiome architecture is shaped by several genetic and environmental factors, including nutrition and physical activity. Physical exercise has preventive or therapeutic effects in respiratory, cardiovascular, neuroendocrine, and muscular diseases. Yet, we still have little information of the beneficial effects of physical exercise on GIT health and microbial composition. Furthermore, we are not aware whether exercise-derived benefits on microbiome diversity can beneficially influence other tissues and body organs. The aim of this article is to review the available literature on exercise-induced microbiome changes and to explain how these changes may induce inflammatory, immune, and oxidative responses that may contribute to the improvement of metabolic disorders. A systemic and comprehensive search of the relevant literature using MEDLINE and Google Scholar databases was conducted during fall 2018 and spring 2019. The search identified sixty-two research and review articles that discussed exercise-induced microbiome changes. The review of the relevant literature suggests that exercise-induced microbial changes affect the host's immune pathways and improve energy homeostasis. Microbes release certain neuroendocrine and immune-modulatory factors that may lower inflammatory and oxidative stress and relieve patients suffering from metabolic disorders. Exercise-induced changes in microbial diversity are able to improve tissue metabolism, cardiorespiratory fitness, and insulin resistance

Viral-Induced Enhanced Disease Illness

Understanding immune responses to viral infections is crucial to progress in the quest for effective infection prevention and control. The host immunity involves various mechanisms to combat viral infections. Under certain circumstances, a viral infection or vaccination may result in a subverted immune system, which may lead to an exacerbated illness. Clinical evidence of enhanced illness by preexisting antibodies from vaccination, infection or maternal passive immunity is available for several viruses and is presumptively proposed for other viruses. Multiple mechanisms have been proposed to explain this phenomenon. It has been confirmed that certain infection- and/or vaccine-induced immunity could exacerbate viral infectivity in Fc receptor- or complement bearing cells- mediated mechanisms. Considering that antibody dependent enhancement (ADE) is a major obstacle in vaccine development, there are continues efforts to understand the underlying mechanisms through identification of the epitopes and antibodies responsible for disease enhancement or protection. This review discusses the recent findings on virally induced ADE, and highlights the potential mechanisms leading to this condition

Colorimetric gold nanoparticles-based assay for direct detection of Clostridium difficile in clinical isolates from Qatar

Clostridium difficile infection (CDI) is a significant health problem worldwide. Control and prevention strategies of C. difficile horizontal transmission require assays with fast detection with high specificity and sensitivity. Conventional diagnostic methods are time consuming and costly for clinical field settings. This study aims to develop gold nanoparticles (AuNPs)-based assay for direct qualitative detection of the nucleic acid of C. difficile and its toxins. A colloidal solution of AuNPs with a diameter of 13±1 nm was prepared and characterized. The qualitative colorimetric AuNPs assay was developed for restricted genomic C. difficile DNA detection, and results were confirmed by PCR. One hundred and five positive C. difficile isolates were collected from patients with diarrheal diseases and tested using AuNPs based-assay. Ninety-six samples (91.4%) were detected positive using AuNPs based assay, as indicated by the color change from red to blue within 1 min. All ninety-six positive samples were positive for toxin B. In conclusion, nano-gold assay prototype was developed for direct and inexpensive detection of C. difficile. The developed prototypes are simple, sensitive, rapid and can substitute PCR-based detection. The developed assay may show potential in the clinical diagnosis of C. difficile, especially in developing countries as it is less costly as compared to the commercially available assays.NPRP award (NPRP 4-1215-3-317) from the Qatar National Research Fun

Biomaterials in Traumatic Brain Injury: Perspectives and Challenges

Traumatic brain injury (TBI) is a leading cause of mortality and long-term impairment globally. TBI has a dynamic pathology, encompassing a variety of metabolic and molecular events that occur in two phases: primary and secondary. A forceful external blow to the brain initiates the primary phase, followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, a rise in oxidative stress, activation of glial cells, and damage to the blood–brain barrier (BBB), resulting in paracellular leakage. Currently, there are no FDA-approved drugs for TBI, but existing approaches rely on delivering micro- and macromolecular treatments, which are constrained by the BBB, poor retention, off-target toxicity, and the complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for the diagnosis and treatment of TBI. Tissue engineering, which includes the use of biomaterials, is one such alternative approach. Biomaterials, such as hydrogels, including self-assembling peptides and electrospun nanofibers, can be used alone or in combination with neuronal stem cells to induce neurite outgrowth, the differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines the inclusion of biomaterials as potential treatments for TBI, including their types, synthesis, and mechanisms of action. This review also discusses the challenges faced by the use of biomaterials in TBI, including the development of biodegradable, biocompatible, and mechanically flexible biomaterials and, if combined with stem cells, the survival rate of the transplanted stem cells. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help to guide the design of future TBI therapies

Epidemiological, Molecular, and Clinical Features of Norovirus Infections among Pediatric Patients in Qatar

Abstract: Background: Norovirus (NoV) is recognized as the second most important etiological agent leading to acute gastroenteritis globally. In order to determine the burden and characteristics of NoV infections in children in Qatar, profiling of circulating genotypes and their correlation with demographics and clinical manifestations were evaluated. Methods: A total of 177 NoV-positive fecal samples were collected from children suffering from acute gastroenteritis (AGE) during two-year period between June 2016 and June 2018. The age of the subjects ranged between 3 months and 12 years (median of 15 months). Genotyping was performed by amplifying and sequencing parts of viral VP1 and RNA-dependent RNA polymerase (RdRp) regions. Phylogenetic analysis and evolutionary relationships were performed using MEGA7.0. Fisher’s exact test was used to run statistical analysis for the clinical and demographical characteristics of circulating strains. Results: Overall, NoV infections were relatively higher in males than females with a ratio of 1.3:1 (p = 0.0073). Most of the NoV infections were reported in children between 1 and 3 years old (49.7%), followed by those 3 years of age (41.2% and 9.1%, respectively). NoV infections occurred throughout the year, with a noticeable increase in summer (36.6%) and drop in winter (25.4%). Nearly all (98.8%) NoV-infected children were positive for genogroup II (GII) compared to only two samples (1.2%) being positive for genogroup I (GI): GI.3 and GI.4. NoV genotype GII.4 (62.2%), GII.2 (15.8%), and GII.3 (13.5%) were predominant in our study. The detected strains shared >98% sequence homology with emerging recombinant strain of GII.P16-GII.4/RUS/Novosibirsk/2017 (MG892929), GII.P16-GII.4 Sydney/2012 (KY887601), GII.4 Sydney/2012, recombinant GII.P4 New Orleans /2009/GII.4 Sydney 2012 (MG585810.1), and the emerging strain GII.P16-GII.2 CHN/2017 (MH321823). Severe clinical illness (vesikari score >10) was reported in children infected with genotypes sharing homology with the above emerging strains. While GII.4 was reported in all age groups, NoV GII.3 infections were higher in children <1 year of age. Both genogroups (GII.4 and GII.3) in addition to GII.2 reported higher incidence in Qatari subjects compared to other nationalities (p = 0.034). Conclusion: This is the first report about NoV molecular epidemiology in Qatar. The most detected NoV strain was genogroup GII, which is the dominant genotype in the Middle East region. Further, we report GII.4, GII.2, and GII.3 as the most predominant NoV genotypes in our study. Moreover, disease severity scores were higher among children genotyped with genogroup GI (GI.4) and genogroup GII (GII.4, GII.2, GII.3, GII.6, and GII.7)

Improving influenza vaccination rate among primary healthcareworkers in Qatar

The purpose of this study was to improve influenza vaccination, and determine factors influencing vaccine declination among health care workers (HCW) in Qatar. We launched an influenza vaccination campaign to vaccinate around 4700 HCW in 22 Primary Health Care Corporation (PHCC) centers in Qatar between 1st and 15th of November, 2015. Our target was to vaccinate 60% of all HCW. Vaccine was offered free of charge at all centers, and information about the campaign and the importance of influenza vaccination was provided to employees through direct communication, emails, and social media networks. Staff were reported as vaccinated or non-vaccinated using a declination form that included their occupation, place of work and reasons for declining the vaccine. Survey responses were summarized as proportional outcomes. We exceeded our goal, and vaccinated 77% of the target population. Only 9% declined to take the vaccine, and the remaining 14% were either on leave or had already been vaccinated. Vaccine uptake was highest among aides (98.1%), followed by technicians (95.2%), and was lowest amongst pharmacists (73.2%), preceded by physicians (84%). Of those that declined the vaccine, 34% provided no reason, 18% declined it due to behavioral issues, and 21% declined it due to medical reasons. Uptake of influenza vaccine significantly increased during the 2015 immunization campaign. This is attributed to good planning, preparation, a high level of communication, and providing awareness and training to HCW with proper supervision and monitoring. 1 2017 by the authors. Licensee MDPI, Basel, Switzerland.Acknowledgments: We would like to thank all staff for participation in the 2015 influenza vaccination campaign at the PHCC. Members of the Health protection at MoPH and PHCC communicable disease control team are highly acknowledged for assistance with implementation. This Study was funded by the Ministry of Public Health.Scopu

Markers associated with covid-19 susceptibility, resistance, and severity

In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity