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Background: Functional Somatic Disorders (FSDs) are characterized by persistent physical symptoms that cannot be explained by other somatic or psychiatric conditions. Multiple Chemical Sensitivity (MCS) is a non-allergic FSD characterized by odour intolerance and various somatic symptoms being attributed to the influence of toxic environmental chemicals in low, usually harmless doses. The pathophysiology of FSDs are still not clear. Smell and taste complaints were also among the notable symptoms characterizing the covid epidemic and the latest evidence suggests overlaps between long COVID and FSDs. Method(s): The study includes advanced analysis of MRI-derived functional and structural connectomes acquired on a 3 T MR scanner. Furthermore, it includes questionnaires and paraclinical tests, e.g. the Sniffin' Stick olfactory test, Mini-Mental State Examination, and Sino-Nasal Outcome test 22. The pilot part of the project included 6 MCS patients who were compared with 6 matched healthy participants. Later follow-up included analysis of 8 multiorgan FSD and 4 post-COVID patients. Result(s): The MCS group showed important brain structural connectivity differences in 34 tracts. Notably, for MCS patients, the olfactory cortex (especially in the right hemisphere) showed decreased connectivity with regions in the emotional system. Conclusion(s): We plan to extend these findings with whole-brain modelling of the functional connectivity in the patient groups. Long-term this could be used as a 'fingerprint' which could help with diagnosis and treatment monitoring in FSDs as well as with new diagnoses such as long-COVID.Copyright © 2023
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Smoking is a significant social problem threatening the population's health, especially during the coronavirus pandemic. Due to the problem's urgency, we present a clinical case of SARS-CoV-2 infection in a patient with 10 years of smoking and concomitant chronic obstructive pulmonary disease (chronic bronchitis and peribronchial pneumosclerosis). Patient L.K., 42 years old, on 13.10.2022, was hospitalized for several hours at the Emergency Hospital of the Ministry of Health of Chuvashia (Cheboksary) with a severe new coronavirus infection. Secondary diagnosis: Chronic obstructive pulmonary disease Case history: for about two to three weeks, the patient noted an increase in body temperature to 37.2-37.4 degreeC and a cough. He has smoked for about 10 years, 1 pack per day. Computed tomography showed signs of bilateral COVID-associated pneumonitis, alveolitis with 85% involvement and consolidation sites, signs of chronic bronchitis, and peribronchial pneumosclerosis. The diagnosis of COVID-19 was confirmed by a polymerase chain reaction in a nasopharyngeal smear. The NEWS2 score was 9. After the treatment started, the patient died. Histological examination showed perivascular sclerosis, peribronchial pneumosclerosis, atrophic changes in the ciliated epithelium, and structural and functional alteration of the bronchial mucosa. In addition, areas of hemorrhage and inflammatory infiltrate in the bronchial wall were found. Coronavirus is known not to cause bronchitis but bronchiolitis. In the presented case, the patient showed signs of transition of bronchitis to the acute stage. Therefore, it can be assumed that the coronavirus acts as a complicating factor. In addition to the described changes, signs of viral interstitial pneumonia, pulmonary edema, and early development of acute respiratory distress syndrome were identified.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.
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Background: SARS-CoV-2 infection is accompanied by acute olfactory disturbance in as high as 70% of cases. This loss is associated with decreased olfactory bulb volume. As time passes, the anosmia tends to subside, but the OB volume decrease does not. Volume reductions in primary and secondary olfactory cortex are also seen following SARS-CoV-2 infection. Nevertheless, concurrent SARS-CoV-2 infection effects on olfactory discrimination, olfactory bulb volume, primary olfactory cortex and its targets have not been investigated. To explore this possibility, we measured olfactory discrimination, olfactory bulb volume, primary olfactory cortex and basal ganglia volume in patients who had SARS-CoV-2 infection more than 12 weeks previously, who were then divided into COVID and long-COVID groups on the basis of selfreported fatigue and concentration complaints. Method(s): This cross-sectional study included 25 post-infection and 19 demographically-matched, no-COVID control participants, we investigated effects on olfaction using NIH Toolbox Odor Identification Test and the Monell Smell Questionnaire. GM structure was assessed with voxel-based morphometry and manual delineation of high resolution (1mm3), T1- and T2-weighted MRI data. Linear regression was used to model group effects on GM structure, adjusting for age, sex, education and total intracranial volume. CAT12/SPM12 and R were used for image processing and statistical modeling. Result(s): Results. The NIH Toolbox Odor Identification Test failed to show differences among the groups. In contrast, the Monell Smell Questionnaire revealed persistently diminished and distorted smell in 50% of the long-COVID sample. Olfactory bulb volume was lower in the long-COVID group (p=0.02). Primary olfactory cortex volume was reduced in the long-COVID group (p=0.004). Caudate volume was also lower in the long-COVID group (p=0.04). Conclusion(s): Conclusions. In the absence of olfactory discrimination problems, long-COVID, but not COVID, patients experience persistent olfactory loss and distortion. These perceptual problems are associated with lower olfactory bulb, primary olfactory cortex, and caudate volume, suggesting that the effects of SARS-CoV-2 infection can extend beyond the olfactory periphery in some cases to affect central targets. (Figure Presented).
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The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) targets mainly the respiratory tract. In addition to respiratory symptoms, many extrapulmonary manifestations were observed in the gastrointestinal tract and reported by SARS-CoV-2 patients, including abdominal pain, nausea, and diarrhea. SARS-CoV-2 binds initially to angiotensin-converting enzyme 2 (ACE2) on the host cell surface via its spike (S) protein before it undergoes endocytosis and fusion with the lysosomal membrane. The spike protein of SARS-CoV-2 is a heavily N- and O-glycosylated trimer. Glycosylation is an essential posttranslational modification in the life cycle of membrane and secretory proteins that affects their structural and functional characteristics as well as their trafficking and sorting patterns. This study aimed at elucidating the impact of glycosylation modulation on the trafficking of both S1 subunit and ACE2 as well as their interaction at the cell surface of intestinal epithelial cells. For this purpose, the S1 protein was expressed in COS-1 cells and its glycosylation modified using N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of ER-located alpha-glucosidases I and II, and or 1-deoxymannojirimycin (dMM), an inhibitor of the Golgi-located alpha-mannosidase I. The intracellular and secreted S1 proteins were analyzed by endoglycosidase H treatment. Similarly, ACE2 trafficking to the brush border membrane of intestinal Caco-2 cells was also assessed in the presence or absence of the inhibitors. Finally, the interaction between the S1 protein and ACE2 was investigated at the surface of Caco-2 cells by co-immunoprecipitation. Our data show that NB-DNJ significantly reduced the secretion of S1 proteins in COS-1 cells, while dMM affected S1 secretion to a lesser extent. Moreover, NB-DNJ and dMM differentially affected ACE2 trafficking and sorting to the brush border membrane of intestinal Caco-2 cells. Strikingly, the interaction between S1 and ACE2 was significantly reduced when both proteins were processed by the glycosylation inhibitors, rendering glycosylation and its inhibitors potential candidates for SARS-CoV-2 treatment. This work has been supported by a grant from the German Research Foundation (DFG) grant NA331/15-1 to HYN. M.K. was supported by a scholarship from the Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI) and by the DFG grant NA331/15-1.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).
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Purpose: Hypertensive disorders of pregnancy (HDP) are associated with longer term postpartum cardiovascular sequelae, including double the risk of ischaemic heart disease and cardiovascular mortality (1). Transthoracic echocardiograms (TTE) were performed in women with pregnancies complicated by gestational hypertension and pre-eclampsia, or uncomplicated pregnancy, at six months and two years postpartum. The aim was to longitudinally assess cardiac structure and function in women with HDP and compare this to women who had a normotensive pregnancy. The six-month results have been previously reported, we now present the two-year data. Method(s): A prospective cohort study was conducted in a pre-specified subgroup of 126 patients within a single, tertiary referral centre as part of the P4 (Post Partum, Physiology, Psychology, and Paediatric Follow Up) study (2). 74 (59%) women had a normotensive pregnancy, and 52 (41%) had a pregnancy complicated by HDP. Women with pre-existing hypertension were excluded from the study. The mean patient age at time of six-month postpartum TTE was 32 years (range 22-47 years). TTEs were performed by blinded experienced sonographers and reported by a single blinded imaging cardiologist. Result(s): Six months postpartum. 126 women underwent TTE at six months postpartum. Although all results fell within normal ranges, compared to women with a normotensive pregnancy, those with HDP had increased left ventricle (LV) wall thickness, higher relative wall thickness, and increased LV mass. E/A ratio was lower, and E/E' ratios higher in the group with pregnancy complicated by HDP, indicating a trend towards poorer diastolic function (2,3). Two years postpartum. 35 women completed a two year postpartum TTE (18 normotensive, 17 HDP). Measurements fell within normal ranges in both groups of women. At two years postpartum, women with HDP had larger BSA (1.9 vs 1.71 2 p=0.003), larger LV internal diastolic diameter (48.4 vs 45.5mm p=0.017) and increased inter-ventricular septum thickness (8.5 vs 7.7mm p=0.007) compared to those with normotensive pregnancy. LV mass was greater in women with HDP (98.1 vs 81.5g), as was LA volume indexed (25.4 vs 23.4 cm3/m3), however these differences did not reach significance (p=0.053 and 0.196 respectively). Compared to normotensive women, those with HDP had higher septal (8.7 vs 7.3 p=0.014) and lateral (6.6 vs 5.4 p=0.017) E/E' ratios, indicating a trend towards diastolic dysfunction. Conclusion(s): Despite measurements falling within normal ranges, our results indicate that women with HDP have changes in cardiac structure and function that persist out to two years postpartum. Limitations exist due to incomplete follow up, leading to small sample size;this was partially due to restrictions on service provision in the context of the COVID-19 pandemic. (Table Presented).
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Background: Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. Method(s): We performed a broad translational investigation, employing brain imaging and cognitive tests in 81 living COVID-19 patients (mildly infected individuals) as well as flow cytometry, respirometry, microscopy, proteomics, and metabolomics in postmortem brain samples, and in preclinical in vitro and ex vivo models. Result(s): We observed orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms in living individuals. Postmortem brain tissue from 26 individuals who died of COVID-19 revealed histopathological signs of brain damage. Five individuals out of the 26 exhibited foci of SARS- CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a non-canonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that significantly reduces neuronal viability. Conclusion(s): Our data support the model in which COVID-19 alter cortical thickness, promoting psychiatric symptoms. In addition, SARS-CoV-2 is able to reach the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients. Funding Source: Sao Paulo Research Foundation (FAPESP) Keywords: COVID-19, Anxiety, Astrocytes, Multi-omics, Brain Magnetic Resonance Imaging (MRI)Copyright © 2023
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T cells, and especially cytotoxic T cells are at the forefront of the fight against viral infection. The killer cells are able not only to distinguish between self and foreign peptides, but also to engage in the fight to clear the viral infection by eliminating the infected cells. Our lab is focused on understanding how T cells engage with viral peptide antigens, that are presented by highly polymorphic HLA molecules. T cells have receptors on their surface called T cell receptors (TCRs) that allow them to recognize the composite surface of the peptide- HLA complex. Using x-ray crystallography we can understand at the atomic level both peptide antigens presentation and TCR recognition, both important to determine the quality of the subsequent immune response. We can then link that structural information with our cellular assay that determines the strength and magnitude of the anti-viral response, providing the basis for peptide modification to reach stronger response or an understanding of viral mutation that led to viral escape. Our current work compared the T cell response, at the antigen level against 32 single epitope derived from spike, between COVID-19 recovered and vaccinated donors. We have shown that the booster shot (3rd dose) increases the antigen-specific T cell response, increases the level of T cell cross-reactivity against variant of SARS-CoV-2, but also alters the phenotype of the T cell. Those results are important to future guide vaccination advise and better understand the immune response to SARS-CoV-2 infection. POSTER PRESENTATIONS Autoimmunity, Infection, Reproduction and Cancer.
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Introduction: The underlying pathophysiology of Post-COVID-19 syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus magnetic resonance spectroscopy (31P-MRS) allows noninvasive assessment of the myocardial energetic state. Purpose(s): We sought to assess whether Post-COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement. Method(s): Prospective case-control study. A total of 20 patients with a clinical diagnosis of Post-COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point. (Figure 1) All patients had been symptomatic with acute COVID-19, but none required hospital admission. Result(s): Between the Post-COVID-19 syndrome patients and matched contemporary controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes, left ventricular mass), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 and extracellular volume [ECV] fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with Post-COVID-19 syndrome showed subepicardial hyperenhancement on the late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, ECV, T1, T2 mapping or energetics. This patient was excluded from statistical analyses. (Table 1) Conclusion(s): In this study, the overwhelming majority of patients with a clinical Post-COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.
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The ongoing outbreak of COVID-19 has become a global health emergency. The SARS-CoV-2 NSP13 helicase plays an important role in SARS-Co V-2 replication and could serve as a target for antivirals to develop potential COVID-19 treatment. The objective of the study is to used Homology modeling and docking analysis of SARS-CoV-2 NSP13 helicase as drug target. The results of this study establish N-[3-( carbamoylamino) phenyl] acetamide as a valuable lead molecule with great potential for SARS-CoV-2 NSP13 helicase inhibitor. The structure and function of SARS-CoV- 2 NSP13 helicase predicted by in silica modeling studies. The SWISS-MODEL Structure Assessment tool was used for homology modeling and visual analysis of the crystal structure of the protein. The validation for structure models was performed using PROCHECK. Model quality estimates based on the QMEAN and ProSA. The MCULE-1-Click docking and InterEvDock-2.0 server were used for proteinlig and docking.The SARS-CoV-2 NSP13 helicase model corresponds to probability confirmation with 90.9% residue of the core section that specifies the accuracy of the predicted model. ProS A Z-score of -9.17;indicates the good quality of the model. Inhibitor N-[3-(carbamoylamino) phenyl] acetamide exhibited effective binding affinity against the NSP13 helicase. The docking results revealed the Lys-146, Leu-147, Ile-151, Tyr-185, Lys-195, Tyr-224, Val-226, Leu- 227, Ser-229 residues exhibit good binding interactions with inhibitor ligand.
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Background: Normal organ function is critically dependent on an intact three-dimensional architecture. Structural abnormalities induced by pathological situations instruct cells to behave abnormally and promoting disease progression oftentimes leading to organ failure. Current approaches do not allow for high-resolution (HR) threedimensional (3D) visualisation and analysis of human organ structure. Method(s): Here, we develop a method to perfuse human tissue segments to remove cells and study the 3D structural scaffold, which could be applied to any organ. Our approach enables HR-3D imaging of organ architecture, which we apply to study healthy and diseased human lung, specifically emphysema, usual interstitial pneumonia, pulmonary sarcoidosis, and COVID-19. Result(s): Our imaging reveals major structural abnormalities previously unseen by existing methodologies. Furthermore, we identify disease-specific patterns of structural remodelling using machine learning, including the altered spatial relationship between extracellular matrix (ECM) proteins collagen type IV, elastin and fibrillar collagen present across all diseases. Conclusion(s): Given the importance of organ structure on function, our approach opens the possibility to understand human physiology in a new way, which may assist in future disease diagnosis and explain the detrimental pulmonary effects of the diseases studied here.
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Background: Novel coronavirus (2019-nCov) imposed deadly health calamity with unexpected disastrous situation alarming the globe for urgent treatment regimes. World Health Organization (WHO) termed the coronavirus disease as COVID-2019 on February 11, 2020 and announced its outbreak as pandemic on 11 March 2020. The first infection was noticed in Wuhan, Hubei province, China, in December 2019, and it is believed that the corona-virus is transmitted to humans through bats as a reservoir involving human to human transfer. However, the proper intermediary transmission channel is yet to be unestablished. Method(s): Elderly populations and patients with concomitant symptoms are more at risk as compared to middle-aged patients as it may progress to pneumonia followed by severe acute respiratory syndrome (SARS) and multi-organ failure. Morbidity rates estimated in patients are less, i.e., 2-3%, but the dearth of a specific treatment strategy to prevent coronavirus infection is a major concern. Result(s): Currently, anti-viral and anti-malarial drugs are in practice for the management of COVID-19 disease along with plasma therapy in the absence of a potent vaccine. Besides, home isolation and social distancing are the precautionary measures adopted by many countries to minimize the spread of infection. Various studies have been conducted, and numerous are still going on to establish specific treatment for COVID-19. Conclusion(s): In this review, we summarized information on the structural components of COVID19 virus with special emphasis on the virus genome, life cycle, the importance of protease enzyme, the role of spike proteins in viral replication, validated drug targets, ongoing effective treatments for COVID-19 management and the latest research on drug design to develop anti-CoV drugs.Copyright © 2021 Bentham Science Publishers.
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SARS-CoV-2 is continually evolving with the emergence of new variants with increased viral pathogenicity. The emergence of heavily mutated Omicron (B.1.1.529) with spike protein mutations are known to mediate its higher transmissibility and immune escape that has brought newer challenges for global public health to contain SARS-CoV-2 infection. One has to come up with a therapeutic strategy against the virus so as to effectively contain the infection and spread. Natural phytochemicals are being considered a significant source of bioactive compounds possessing an antiviral therapeutic potential. Being a promising anticancer and chemo-preventive agent, Silybin holds a significant potential to be used as a therapeutic. In the present study, molecular docking of Silybin with Omicron spike protein (7QNW) was carried out. Molecular docking results showed greater stability of Silybin in the active site of the Omicron spike protein with suitable binding mode of interactions. The study reveals that Silybin has the potential to block the host ACE2 receptor-viral spike protein binding;thereby inhibiting the viral entry to human cells. Therefore, Silybin may be further developed as a medication with the ability to effectively combat SARS-CoV-2 Omicron.Copyright © The Author(s) 2023.
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Background Many patients with COVID-19, particularly from the pandemic's early phase, have been reported to have evidence of cardiac injury such as cardiac symptoms, troponinemia, or imaging or ECG abnormalities during their acute course. Cardiac magnetic resonance (CMR) has been particularly useful to assess myocardial abnormalities given its comprehensive characterization of structure, function, and tissue. Overall, findings have varied, and long term impact of COVID-19 on myocardial structure and function needs further elucidation. Methods We performed TTE and 3T CMR with gadoterate meglumine (Clariscan, GE Healthcare) in survivors of the initial stage of the pandemic without preexisting cardiac disease and matched controls at long-term follow up?>6 months after infection, using an array of techniques to comprehensively evaluate the myocardium. Chi square tests for categorical and t tests for continuous variables were used. P <0.05 was considered significant. Results Our study population consisted of 40 COVID survivors and 12 controls of similar age, sex and race-ethnicity distribution with median age 46, 50% female, 48% Hispanic, 28% Black, mean BMI 27. None had presented with thromboembolism, myocarditis, or ischemia;35% had been hospitalized with 28% intubated. Imaging was performed median 308 days after initial infection. We found no difference in echo characteristics including measures of LV and RV structure and systolic function, valvular abnormalities, or LV diastolic function with median LVEF 60% v 58%, LVEDD 4.0 v 4.4, E/e' ~6, and no RWMA in either group. Using CMR, we confirmed no differences in LV and RV structure and function including median LVEF 57% v 58%, RVEF 53% v 53%, LVEDVi 74 v 72, and RVEDVi 77 v 74. We found no significant differences in T1 (1305 v 1280), T2 (46 v 47), ECV (29 v 30), or LGE mapping. With analysis stratified by patient hospitalization status as an indicator of COVID severity, no differences were uncovered. Conclusion Multimodal imaging of a diverse cohort of COVID-19 survivors who had not presented with acute cardiac pathology reveals no distinct features indicating long-lasting structural or functional damage or inflammation of the myocardium.Copyright © 2023 American College of Cardiology Foundation
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The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.Copyright © 2021, IAS-USA. All rights reserved.
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As of 1st of September 2020, the COVID-19 pandemic has reached an unprecedented level of more than 25 million cases with more than 850,000 deaths. Moreover, all the drug candidates are still undergoing testing in clinical trials. In this regard, a breakthrough in drug design is neces-sary. One strategy to devise lead compounds is leveraging natural products as a lead source. Sever-al companies and research institutes are currently developing anti-SARS-CoV-2 lead from natural products. Flavonoids are well known as a class of antiviral compounds library. The objective of this research is to employ virtual screening methods for obtaining the best lead compounds from the library of flavonoid compounds. This research employed virtual screening methods that com-prised of downloading the protein and lead compound structures, QSAR analysis prediction, itera-tions of molecular docking simulation, and ADME-TOX simulation for toxicity prediction. The QSAR analysis found that the tested compounds have broad-spectrum antiviral activity, and some of them exhibit specific binding to the 3C-like Protease of the Coronavirus. Moreover, juglanin was found as the compound with the fittest binding with the Protease enzyme of SARS-CoV-2. Al-though most of the tested compounds are deemed toxic by the ADME-Tox test, further research should be conducted to comprehend the most feasible strategy to deliver the drug to the infected lung cells. The juglanin compound is selected as the fittest candidate as the SARS-CoV-2 lead compound in the tested flavonoid samples. However, further research should be conducted to observe the lead delivery method to the cell.Copyright © 2021 Bentham Science Publishers.
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In 2012, a coronavirus was isolated from a patient with severe pneumonia. This beta-coronavirus, which appeared in Saudi Arabia, was named Middle East Respiratory Syndrome Coro-navirus (MERS-CoV). MERS-CoV is the sixth identified coronavirus that has the ability to infect humans. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is a zoonotic pathogen transmitted between animals and humans. To date, MERS-CoV is responsible for an epidemic that is still ongoing, but limited to the Arabian Peninsula, with a total number of more than 2000 cases identified and a mortality rate of around 35%. The largest outbreaks of human-to-human transmission were reported in Jeddah in 2014 and South Korea in 2015. This infection causes a high mortality rate and no vaccine or medical countermeasures are currently available. Currently, no specific treatment or vaccine is available against this virus. The current challenge is to contain the epidemic and continue research efforts to develop a vaccine and a treatment. Certain flavonoids inhibit the replication of viral RNA and have therapeutic potential against viruses and bacteria. Therefore, it is suggested that flavonoids with these characteristics can be used as models to develop potent inhibi-tors of MERS-CoV. This work reviews current knowledge and provides an update on MERS-CoV and MERS-CoV 3Clpro virology, epidemiology, clinical features, and the use of flavonoids as potential inhibitors and therapeutic agents for MERS-CoV, and MERS-CoV 3Clpro. This review tries to elucidate the structure-activity relationships (SAR) of varied polyphenols against MERS-CoV 3C-like protease (3Clpro).Copyright © 2022 Bentham Science Publishers.
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Background: Post COVID19 condition occurs in individuals with a history of probable or confirmed SARS Cov2 infection, usually 3 months from the onset of COVID19 with symptoms that last for up to at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction, but also arterial hypertension (AH) and generally have an impact on everyday function. Aim: COVID 19 pneumonia initiates new onset AH and aggravates the structural and functional myocardium remodeling in the long term after hospitalization. Methods: The study population /initially questioned 1500 patients for symptoms after acute COVID 19 pneumonia / included 220 patients without history of any disease, mean age of 45 ± 12 years, male 145 (43 ± 10 years) female 75 (52 ± 14 years). The global longitudinal strain (GLS) was extracted for left ventricle (LV) and right ventricle(RV) and AMBP analysis, mean arterial pressure (MAP)and heart rate HR were performed at baseline /30-40 days after acute infection/ 3rd and 12th months follow up. CMR was performed at 3rd (3mFU) and 12th months (12mFU) also to confirm our resulst. Results: From initial population /1500 pts/ self-reported symptoms at 12mFU are 1265 (84.6 %) and 235 /15.4 %) are symptom free at 12mFU. At 3mFU HR and MAP increased significantly / from 75 ± 6 beats /min to 88 ± 12 beats/ min, 109 ± 15 mmHg to 118 ± 19mmHg. Sys BP increased slightly at 3mFU /128 ± 14, p = 0.6/ and continue at 12mFU / 129 ± 12, p = 0.7/. Diastolic BP increased significantly at 12mFU /86 ± 12.3 to 91 ± 10.0, p > 0.01/ and AH presence at 3mFU in 143 (65%)up to 161(73%) at 12mFU. Symptoms of heart failure with preserved EF were found at 3mFU in 91 pts (41%) and in 99 pts (45%) at 12mFU. Echocardiography showed predominantly decrease of the load on the right heart at 3mFU and 12mFU (RV FAC % p < 0.019, TAPSE p < 0.05, RVOT VTI p < 0.01). LV function showd increased EDD, ESD, EDV, ESV, and decreased EF and GLS at 3mFU and slightly improvement at 12mFU. Despite normal EF, GLS / 18.5 %, p < 0.01) and segmental LS in all apical and mid anteroseptal, inferoseptal and basal anteroseptal and inferoseptal levels (16% to 18%, p < 0.01) and RV (22.3% to 24%) at 12mFU shown diminished and still preserved values. Conclusion: New onset AH is one of major symptoms after COVID 19 and remains at 12mFU. Despite of satisfactory improvement of conventional parameters for LV and RV function, GLS indicate worsening of the LV systolic function.
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The main aim of this study is to determine the bioactive compounds which have drug-like properties and has the potential to combat the spike-glycoprotein of SARS-CoV-2. The 6LXT protein of covid-19 was chosen from the protein data bank as a target protein. The compounds which are potentially capable to bind with the target were picked from the PubChem database and docked using the tool Autodock 4.2. Molecular docking of the molecules was done with the best conformations of the ligands and grid size was selected according to the hit compounds' interaction with the target protein. The ligand binding sites with the target molecules were predicted using MetaPocket 2.0. The docking Score of 50 compounds wascarried out and also toxicity studies were carried out. The compounds selected were calculated to identify the best conformations having drug-likeness properties. The top 10 compounds were chosen for the structure-activity relationship based on their binding interactions with the protein and ligand. The ligands then underwent the pharmacokinetic analysis followed by Lipinski's and all the results were finalized and categorized. ManzamineA, Imatinib, and basotinib were elected as the peak compounds with the binding energy -9.01kcal/mol, -8.71kcal/mol, and -8.01kcal/mol.
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Aptamers are single-stranded DNA or RNA oligonucleotides that can selectively bind to a specific target. They are generally obtained by SELEX, but the procedure is challenging and time-consuming. Moreover, the identified aptamers tend to be insufficient in stability, specificity, and affinity. Thus, only a handful of aptamers have entered the practical use stage. Recently, computational approaches have demonstrated a significant capacity to assist in the discovery of high-performance aptamers. This review discusses the advances achieved in several aspects of computational tools in this field, as well as the new progress in machine learning and deep learning, which are used in aptamer identification and optimization. To illustrate these computationally aided processes, aptamer selections against SARS-CoV-2 are discussed in detail as a case study. We hope that this review will aid and motivate researchers to develop and utilize more computational techniques to discover ideal aptamers effectively. Copyright © 2022 Elsevier B.V.