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

How could artificial intelligence aid in the fight against coronavirus?: An interview with Dr Hadi M Yassine and Dr Zubair Shah by Felicity Poole, Commissioning Editor

[No abstract available

Characterization of an H3N2 triple reassortant influenza virus with a mutation at the receptor binding domain (D190A) that occurred upon virus transmission from turkeys to pigs

The hemagglutinin (HA) protein of influenza virus mediates essential viral functions including the binding to host receptor and virus entry. It also has the antigenic sites required for virus neutralization by host antibodies. Here, we characterized an H3N2 triple reassortant (TR) influenza virus (A/turkey/Ohio/313053/04) with a mutation at the receptor binding domain (Asp190Ala) that occurred upon virus transmission from turkeys to pigs in an experimental infection study. The mutant virus replicated less efficiently than the parental virus in human, pig and turkey primary tracheal/bronchial epithelial cells, with more than 3-log10 difference in virus titer at 72 hours post infection. In addition, the mutant virus demonstrated lower binding efficiency to plasma membrane preparations from all three cell types compared to the parental virus. Antisera raised against the parental virus reacted equally to both homologous and heterlogous viruses, however, antisera raised against the mutant virus showed 4-8 folds lower reactivity to the parental virus

Assessment of Indoor Air Quality of Four Primary Health Care Centers in Qatar.

Airborne bacteria pose a potential risk to human health upon inhalation in the indoor environments of health care facilities. Airborne bacteria may originate from various sources, including patients, workers, and daily visitors. Hence, this study investigates the quantity, size, and identification of airborne bacteria indoors and outdoors of four Primary Health Care Centers (PHCC) in Doha, Qatar. Air samples were collected from the lobby, triage room, and outside environment of the centers, including, Qatar University (QU-HC), Al-Rayyan (AR-HC), Umm-Ghuwailina (UG-HC), and Old Airport (OA-HC) between August 2020 and March 2021, throughout both the hot and the cold seasons. Samples were collected using an Anderson six-stage cascade impactor. The mean of the total colony-forming units was calculated per cubic meter of air (CFU/m). QU-HC had the lowest mean of total bacterial count compared with other centers in the indoor and outdoor areas with 100.4 and 99.6 CFU/m, respectively. In contrast, AR-HC had the highest level, with 459 CFU/m indoors, while OA-HC recorded the highest bacterial concentration of the outdoor areas with a total mean 377 CFU/m. In addition, 16S rRNA sequencing was performed for genera identification. , , , and were the four most frequently identified bacterial genera in this study. The abundance of airborne bacteria in the four health centers was higher in the cold season. About 46% of the total airborne bacterial count for three PHCC centers exceeded 300 CFU/m, making them uncompliant with the World Health Organization's (WHO) recommendation for indoor settings. Consequently, an IAQ standards should be shaped to establish a baseline for measuring air pollution in Qatar. Additionally, it is crucial to understand seasonal fluctuations better so that hospitals can avoid rising and spreading infection peaks.This research was funded partially by Primary Health Care Corporation, grant number PHCC/RC/18/06/002

Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses

The triple reassortant H3N2 viruses were isolated for the first time from pigs in 1998 and are known to be endemic in swine and turkey populations in the United States. In 2004, we isolated two H3N2 triple reassortant viruses from two turkey breeder flocks in Ohio and Illinois. Infected hens showed no clinical signs, but experienced a complete cessation of egg production. In this study, we evaluated three triple reassortant H3N2 isolates of turkey origin and one isolate of swine origin for their transmission between swine and turkeys. Although all 4 viruses tested share high genetic similarity in all 8 genes, only the Ohio strain (A/turkey/Ohio/313053/04) was shown to transmit efficiently both ways between swine and turkeys. One isolate, A/turkey/North Carolina/03, was able to transmit from pigs to turkeys but not vice versa. Neither of the other two viruses transmitted either way. Sequence analysis of the HA1 gene of the Ohio strain showed one amino acid change (D to A) at residue 190 of the receptor binding domain upon transmission from turkeys to pigs. The Ohio virus was then tested for intraspecies transmission in three different avian species. The virus was shown to replicate and transmit among turkeys, replicate but does not transmit among chickens, and did not replicate in ducks. Identifying viruses with varying inter- and intra-species transmission potential should be useful for further studies on the molecular basis of interspecies transmission

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

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus’s transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough

Immunomodulation Induced by Host Pathogen Interaction

Controlling and preventing infections require deep understanding of the complex interplay that occurs between the host and pathogen following infection. In essence, immunomodulation is any process leading to an immune response that can be altered to a desired level. In mammals, the immune system has developed an extensive array of cells and immunomodulators to recognize, identify, and eliminate foreign invaders. On the other hand, pathogens have evolved multiple mechanisms to combat the host immune system as they establish infections. In this context and under certain circumstances, an infection may result in a subverted immune system, which may lead to an exacerbated illness. Recent advances in biotechnology have enhanced our knowledge of the complex interplay that occurs between the host and invading pathogens following infection, through understanding of the microbial virulence strategies as well as the host’s approaches to combat the infection

Profiling the Oral Microbiome and Plasma Biochemistry of Obese Hyperglycemic Subjects in Qatar

The present study is designed to compare demographic characteristics, plasma biochemistry, and the oral microbiome in obese ( = 37) and lean control ( = 36) subjects enrolled at Qatar Biobank, Qatar. Plasma hormones, enzymes, and lipid profiles were analyzed at Hamad Medical Cooperation Diagnostic Laboratory. Saliva microbiome characterization was carried out by 16S rRNA amplicon sequencing using Illumina MiSeq platform. Obese subjects had higher testosterone and sex hormone-binding globulin (SHBG) concentrations compared to the control group. A negative association between BMI and testosterone ( < 0.001, r = -0.64) and SHBG ( < 0.001, r = -0.34) was observed. Irrespective of the study groups, the oral microbiome was predominantly occupied by , , and species. A generalized linear model revealed that the Firmicutes/Bacteroidetes ratio (2.25 ± 1.83 vs. 1.76 ± 0.58; corrected -value = 0.04) was higher, and phylum Fusobacteria concentration (4.5 ± 3.0 vs. 6.2 ± 4.3; corrected -value = 0.05) was low in the obese group compared with the control group. However, no differences in microbiome diversity were observed between the two groups as evaluated by alpha (Kruskal-Wallis ≥ 0.78) and beta (PERMANOVA = 0.37) diversity indexes. Certain bacterial phyla (Acidobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Firmicutes/Bacteroidetes) were positively associated ( = 0.05, r ≤ +0.5) with estradiol, fast food consumption, creatinine, breastfed during infancy, triglycerides, and thyroid-stimulating hormone concentrations. In conclusion, no differences in oral microbiome diversity were observed between the studied groups. However, the Firmicutes/Bacteroidetes ratio, a recognized obesogenic microbiome trait, was higher in the obese subjects. Further studies are warranted to confirm these findings in a larger cohort.Qatar National Research Fun