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1.
J Mol Struct ; 1229: 129829, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-2095817

ABSTRACT

A series of hybrid indolo[3,2-c]isoquinoline (δ-carboline) analogs incorporating two pyrimidine and piperizine ring frameworks were synthesized. Intending biological activities and SAR we propose replacements of fluorine, methyl and methoxy of synthetic compounds for noteworthy antimicrobial, antioxidant, anticancer and anti-tuberculosis activities. Among these compounds 3a, 4a and 5e were progressively strong against E. coli and K. pneumonia. Whereas, compounds 4a, 5a and 6a with addition of various functional groups (OCH3, CH3) were excellent against S. aureus and B. subtilis. Compound 5c exhibited strong RSA and dynamic ferrous ion (Fe2+) metal chelating impact with IC50 of 7.88 ± 0.93 and 4.06 ± 0.31 µg/mL, respectively. Compound 5e was considerably cytotoxic against all cancer cells displaying activity better than the standard drug. Compounds 6b and 6e inhibited M. tuberculosis (MIC 1.0 mg/L) considerably. Molecular docking studies indicate that compounds 4d, 5a, 5b, 6b and 6f exhibited good interactions with 6LZE (COVID-19) and 6XFN (SARS-CoV-2) at active sites. The structure of the synthesized compounds were elementally analyzed using IR, 1H, 13C NMR and mass spectral information.

2.
Eur J Neurol ; 28(10): 3443-3447, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1607745

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long-lasting, COVID-19-related brain injury develops in acute respiratory distress syndrome patients after life-saving re-oxygenation. METHODS: Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non-COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non-targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry. RESULTS: Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro-pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3-month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+. CONCLUSIONS: Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re-oxygenation and lifestyle factors might influence long-lasting brain injuries in a context of foodborne micro-pollutants.


Subject(s)
COVID-19 , Delirium , Environmental Pollutants , Brain/diagnostic imaging , Critical Care , Humans , SARS-CoV-2
3.
Cardiovasc Res ; 117(9): 2045-2053, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1526155

ABSTRACT

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.


Subject(s)
Aortic Diseases , Biomedical Research/trends , Peripheral Vascular Diseases , Animals , Aortic Diseases/diagnosis , Aortic Diseases/epidemiology , Aortic Diseases/genetics , Aortic Diseases/therapy , COVID-19 , Clinical Trials as Topic , Diffusion of Innovation , Humans , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/epidemiology , Peripheral Vascular Diseases/genetics , Peripheral Vascular Diseases/therapy , Prognosis
4.
Polymers (Basel) ; 13(7)2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1305779

ABSTRACT

Chitosan is broadly used as a biological material since of its excellent biological activities. This work describes investigations of chitosan interaction with SARS-CoV-2, which is occupied by human respiratory epithelial cells through communication with the human angiotension-converting enzyme II (ACE2). The ß-chitosan derivatives are synthesized and characterized by FT-IR, nuclear magnetic resonance (1H and 13C NMR), mass spectrometry, X-ray diffraction, TGA, DSC, and elemental analysis. The ß-chitosan derivatives were screened for cytotoxic activity against the HepG2 and MCF-7 (breast) cancer cell lines. Compound 1h (GI50 0.02 µM) is moderately active against the HepG2 cancer cell line, and Compound 1c is highly active (GI50 0.01 µM) against the MCF-7 cancer cell line. In addition, chitosan derivatives (1a-1j) docking against the SARS coronavirus are found by in-silico docking analysis. The findings show that compound 1c exhibits notable inhibition ability compared with other compounds, with a binding energy value of -7.9 kcal/mol. Based on the molecular docking results, the chitosan analog is proposed to be an alternative antiviral agent for SARS-CoV2.

5.
Indian J Ophthalmol ; 69(7): 1915-1927, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278615

ABSTRACT

Coronavirus disease-associated mucormycosis (CAM) is an established clinical entity in India. In the past 4 months, there has been a sharp upsurge in the number of CAM cases in most parts of the country. Early diagnosis can be lifesaving. Magnetic resonance imaging (MRI) imaging remains the corner stone of management in patients with ROCM. This review discussed the utility of MRI imaging in ROCM with an emphasis on the ideal MRI protocol in a suspected case of ROCM, the pathways of spread of infection, the classic diagnostic features, MRI for staging of the disease, MRI for prognostication, MRI for follow up, and imaging features of common differentials in ROCM. The pit falls of MRI imaging and a comparison of CT and MRI imaging in ROCM are discussed. The clinical interpretation of areas of contrast uptake and those of necrosis and its relevance to treatment are discussed. This review aims to familiarize every member of the multidisciplinary team involved in managing these patients to be able to interpret the findings on MRI in ROCM.


Subject(s)
Mucormycosis , Nose Diseases , Orbital Diseases , Antifungal Agents/therapeutic use , Humans , India , Magnetic Resonance Imaging , Mucormycosis/diagnostic imaging , Nose Diseases/drug therapy , Orbital Diseases/diagnostic imaging , Orbital Diseases/drug therapy
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 261: 120006, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1243222

ABSTRACT

Investigation the molecular structure of the system requires a detailed experience in dealing with theoretical computational guides to highlight its important role. Molecular structure of three heterocyclic compounds 8,10-diphenylpyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (HL), 8-phenyl-10-(p-tolyl)pyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (CH3L) and10-(4-nitrophenyl)-8-phenylpyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (NO2L) was studied at DFT/B3LYP/6-31G (d,p) level in ethanol solvent. Spectroscopic properties such Infrared (IR, 1H NMR and 13C NMR) and ultraviolet-visible (UV-VIS) analyses were computed. Some quantum and reactivity parameters (HOMO energy, LUMO energy, energy gap, ionization potential, electron affinity, chemical potential, global softness, lipophelicity) were studied, also molecular electrostatic potential (MEP) was performed to indicate the reactive nucleophilic and electrophilic sites. The effects of H-, CH3- and NO2- substituents on heterocyclic ligands were studied and it was found that the electron donation sites concerned with hydrogen and methyl substituents over nitro substituent. Topological analysis using reduced density gradient (RDG) was discussed in details. To predict the relevant antiviral activity of the reported heterocyclic compounds, molecular docking simulation was applied to the crystal structure of SARS-Cov-2 viral Mpro enzyme with 6WTT code and PLpro with 7JRN code. The enzymatic viral protein gives an image about the binding affinity between the target protein receptor and the heterocyclic ligands entitled. The hydrogen bonding interactions were evaluated from molecular docking with different strength for each ligand compound to discuss the efficiency of heterocyclic ligands toward viral inhibition.


Subject(s)
COVID-19 , Thiones , Humans , Molecular Docking Simulation , Molecular Structure , Pyrimidines , SARS-CoV-2 , Spectroscopy, Fourier Transform Infrared
7.
Bioorg Chem ; 112: 104967, 2021 07.
Article in English | MEDLINE | ID: covidwho-1213051

ABSTRACT

Nowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world's economy and the worldwide health sector. The present work is an investigation of the newly synthesized 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine (M1BZP) molecule's inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. M1BZP crystallizes in monoclinic type with P1211 space group. For the title compound M1BZP, spectroscopic characterization like 1H NMR, 13C NMR, FTIR, were carried out. The geometry of the compound had been optimized by the DFT method and its results were compared with the X-ray diffraction data. The calculated energies for the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) showed the stability and reactivity of the title compound. Intermolecular interactions in the crystal network were determined using Hirshfeld surface analyses. The molecular electrostatic potential (MEP) picture was drawn using the same level of theory to visualize the chemical reactivity and charge distribution on the molecule. Molecular docking study performed for the synthesized compound revealed an efficient interaction with the COVID-19 protease and resulted in good activities. We hope the present study would help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus. Virtual ADME studies were carried out as well and a relationship between biological, electronic, and physicochemical qualifications of the target compound was determined. Toxicity prediction by computational technique for the title compound was also carried out.


Subject(s)
Antiviral Agents/metabolism , Piperidines/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/analogs & derivatives , Alanine/chemistry , Alanine/metabolism , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Binding Sites , COVID-19/pathology , COVID-19/virology , Crystallography, X-Ray , Density Functional Theory , Half-Life , Humans , Molecular Conformation , Molecular Docking Simulation , Piperidines/chemical synthesis , Piperidines/metabolism , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/metabolism , Viral Matrix Proteins/antagonists & inhibitors , Viral Matrix Proteins/metabolism
8.
Surg Neurol Int ; 12: 166, 2021.
Article in English | MEDLINE | ID: covidwho-1202111

ABSTRACT

BACKGROUND: In the aftermath of COVID-19 outbreak, there is a strong need to find strategies to monitor SARSCoV-2 transmission. While the application of screening techniques plays a major role to this end, there is evidence challenging the real significance of seroconversion. We reported a case of COVID-19 reactivation associated with a neurosurgical operation with early neuropsychiatric involvement presumably promoted by olfactory and gustatory impairment in the first infection. CASE DESCRIPTIO: A 57-year-old man was referred for a 2-month history of progressive development of imbalance, dizziness, and vomiting. Magnetic resonance imaging showed two bilateral hemispheric cerebellar lesions. In line with our triage protocol, the patient underwent a nasopharyngeal swab for RNA of SARS-CoV-2 detection, which resulted positive. Of note, the patient had reported in the previous month hyposmia and hypogeusia. After a period of 14 days, three new swabs were performed with negative results, leading the way to surgery. In the early post-operative period, the patient manifested acute onset of psychotic symptoms with hyperactive delirium, followed by fever and acute respiratory failure. A chest computed tomography revealed a specific pattern of ground-glass opacities in the lower lobes bilaterally, suggesting a viral pneumonia. Serological tests demonstrated the seroconversion and a new nasopharyngeal swab confirmed SARS-CoV-2 infection. CONCLUSION: Our report highlights the importance of comprehensive screening assessments in sensitive cases highly susceptible to COVID-19 recurrence.

9.
Chronobiol Int ; 38(8): 1120-1134, 2021 08.
Article in English | MEDLINE | ID: covidwho-1180371

ABSTRACT

The influence of low intensity electromagnetic fields on circadian clocks of cells and tissues has gained increasing scientific interest, either as a therapeutic tool or as a potential environmental hazard. Nuclear Magnetic Resonance (NMR) refers to the property of certain atomic nuclei to absorb the energy of radio waves under a corresponding magnetic field. NMR forms the basis for Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy and, in a low-intensity form, for NMR therapy (tNMR). Since the circadian clock is bi-directionally intertwined with hypoxic signaling in vertebrates and mammals, we hypothesized that low intensity electromagnetic fields, such as tNMR, might not only affect circadian clocks but also Hypoxia-Inducible Factor-1α (HIF-1α). As master regulator of the hypoxic signaling pathway, HIF-1α is known to dampen the circadian amplitude under reduced oxygen availability, while the hypoxic response of cells and organisms, itself, is tightly clock controlled. In a first experiment, we investigated if tNMR is able to act as Zeitgeber for the core clock mechanism of unsynchronized zebrafish and mouse fibroblast cells, using direct light irradiation and treatment with the glucocorticoid Dexamethasone as references. tNMR significantly affected the cell autonomous clocks of unsynchronized mouse fibroblast cells NIH3-T3, but did not act as a Zeitgeber. Similar to light irradiation and in contrast to treatment with Dexamethasone, tNMR did not synchronize expression profiles of murine clock genes. However, irradiation with tNMR as well as light significantly altered mRNA and protein expression levels of Cryptochrome1, Cryptochrome2 and Clock1 for more than 24 h. Changes in mRNA and protein after different treatment durations, namely 6 and 12 h, appeared to be nonlinear. A nonlinear dose-response relationship is known as hallmark of electromagnetic field induced effects on biological systems. The most prominent alterations were detected in murine HIF-1α protein, again in a nonlinear dose-response. In contrast to murine cells, zebrafish fibroblasts did not respond to tNMR at all. Light, a potent Zeitgeber for the peripheral clocks of fish, led to the expected synchronized clock gene oscillations of high amplitude, as did Dexamethasone. Hence, we conclude, mammalian peripheral clocks are more susceptible to tNMR than the direct light entrainable fish fibroblasts. Although light and tNMR did not act as Zeitgebers for the circadian clocks of unsynchronized murine cells, the significant observed effects might indicate downstream cell-physiological ramifications, which are worth future investigation. However, beside the effects tNMR exerts on the core clock mechanism of mammalian cells, the technology might be the first non-pharmacological approach to modify HIF-1α protein in cells and tissues. HIF-1α and the associated circadian clock play key roles in diseases with underlying ischemic background, such as infarct, stroke, and cancer and, also infectious diseases, such as Covid-19. Hence, low intensity magnetic fields such as tNMR might be of significant medical interest.


Subject(s)
Circadian Clocks , Electromagnetic Fields , Hypoxia-Inducible Factor 1/metabolism , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , 3T3 Cells , Animals , Circadian Rhythm , Electromagnetic Fields/adverse effects , Fibroblasts , Humans , Hypoxia/metabolism , Magnetic Resonance Imaging/adverse effects , Magnetic Resonance Spectroscopy/adverse effects , Mice , Time Factors , Zebrafish
10.
Germs ; 11(1): 111-115, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1159528

ABSTRACT

INTRODUCTION: Several publications described neurological manifestations caused by SARS-CoV-2. Immune-mediated neurological damages caused by COVID-19 are increasingly recognized. CASE REPORT: A young male presented in March 2020 with a new-onset seizure. Later, he started to experience a severe headache. During the second admission in May, the MRI of the brain showed left frontal lesion. Nasal PCR for SARS-CoV-2 was negative, but the serology was positive, raising the suspicion of immune-mediated encephalitis. Elevated cerebrospinal fluid immunoglobulin G with two oligoclonal bands were also seen. The patient received IV immunoglobulin and showed improvement in headache. Follow-up MRIs of the brain revealed complete resolution of the lesion. DISCUSSION: Neurological complications from COVID-19 have been increasingly recognized. The proposed pathophysiology is either direct damage of neurological tissues, or indirectly through immune-mediated mechanisms. The timeline of the patient's presentation with seizure, as well as the lesion on the brain MRI with complete resolution after the IV immunoglobulin, strongly suggest that the patient had immune-mediated encephalitis after exposure to SARS-CoV-2. CONCLUSIONS: Several cases of encephalitis caused by SARS-CoV-2 have been reported. Immune-mediated encephalitis as probable pathophysiology is described here.

11.
Sens Actuators B Chem ; 337: 129786, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1146819

ABSTRACT

The rapid and sensitive diagnosis of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the crucial issues at the outbreak of the ongoing global pandemic that has no valid cure. Here, we propose a SARS-CoV-2 antibody conjugated magnetic graphene quantum dots (GQDs)-based magnetic relaxation switch (MRSw) that specifically recognizes the SARS-CoV-2. The probe of MRSw can be directly mixed with the test sample in a fully sealed vial without sample pretreatment, which largely reduces the testers' risk of infection during the operation. The closed-tube one-step strategy to detect SARS-CoV-2 is developed with home-made ultra-low field nuclear magnetic resonance (ULF NMR) relaxometry working at 118 µT. The magnetic GQDs-based probe shows ultra-high sensitivity in the detection of SARS-CoV-2 due to its high magnetic relaxivity, and the limit of detection is optimized to 248 Particles mL‒1. Meanwhile, the detection time in ULF NMR system is only 2 min, which can significantly improve the efficiency of detection. In short, the magnetic GQDs-based MRSw coupled with ULF NMR can realize a rapid, safe, and sensitive detection of SARS-CoV-2.

12.
Rofo ; 193(8): 937-946, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1139768

ABSTRACT

OBJECTIVES: As a cross-section discipline within the hospital infrastructure, radiological departments might be able to provide important information regarding the impact of the COVID-19 pandemic on healthcare. The goal of this study was to quantify changes in medical care during the first wave of the pandemic using radiological examinations as a comprehensive surrogate marker and to determine potential future workload. METHODS: A retrospective analysis of all radiological examinations during the first wave of the pandemic was performed. The number of examinations was compared to time-matched control periods. Furthermore, an in-depth analysis of radiological examinations attributed to various medical specialties was conducted and postponed examinations were extrapolated to calculate additional workload in the near future. RESULTS: A total of 596,760 examinations were analyzed. Overall case volumes decreased by an average of 41 % during the shutdown compared to the control period. The most affected radiological modalities were sonography (-54 %), X-ray (-47 %) followed by MRI (-42 %). The most affected medical specialty was trauma and orthopedics (-60 % case volume) followed by general surgery (-49 %). Examination numbers increased during the post-shutdown period leading to a predicted additional workload of up to 22 %. CONCLUSION: This study shows a marked decrease in radiological examinations in total and among several core medical specialties, indicating a significant reduction in medical care during the first COVID-19 shutdown. KEY POINTS: · Number of radiological examinations decreased by 41 % during the first wave of the COVID-19 pandemic.. · Several core medical specialties were heavily affected with a reduction of case volumes up to 60 %.. · When extrapolating postponed examinations to the near future, the overall workload for radiological departments might increase up to 22 %.. CITATION FORMAT: · Fleckenstein FN, Maleitzke T, Böning G et al. Decreased Medical Care During the COVID-19 Pandemic - A Comprehensive Analysis of Radiological Examinations. Fortschr Röntgenstr 2021; 193: 937 - 946.


Subject(s)
COVID-19 , Pandemics , Radiography , Radiology Department, Hospital , Radiology , Workload , Delivery of Health Care , Humans , Orthopedics , Radiography/trends , Radiology/trends , Retrospective Studies
13.
Clin Radiol ; 76(5): 391.e33-391.e41, 2021 05.
Article in English | MEDLINE | ID: covidwho-1131209

ABSTRACT

AIM: To evaluate the lung function of coronavirus disease 2019 (COVID-19) patients using oxygen-enhanced (OE) ultrashort echo time (UTE) MRI. MATERIALS AND METHODS: Forty-nine patients with COVID-19 were included in the study. The OE-MRI was based on a respiratory-gated three-dimensional (3D) radial UTE sequence. For each patient, the percent signal enhancement (PSE) map was calculated using the expression PSE = (S100% - S21%)/S21%, where S21% and S100% are signals acquired during room air and 100% oxygen inhalation, respectively. Agreement of lesion detectability between UTE-MRI and computed tomography (CT) was performed using the kappa test. The Mann-Whitney U-test was used to evaluate the difference in the mean PSE between mild-type COVID-19 and common-type COVID-19. Spearman's test was used to assess the relationship between lesion mean PSE and lesion size. Furthermore, the Mann-Whitney U-test was used to evaluate the difference in region of interest (ROI) mean PSE between normal pulmonary parenchyma and lesions. The Kruskal-Wallis test was applied to test the difference in the mean PSE between different lesion types. RESULTS: CT and UTE-MRI reached good agreement in lesion detectability. Ventilation measures in mild-type patients (5.3 ± 5.5%) were significantly different from those in common-type patients (3 ± 3.9%). Besides, there was no significant correlation between lesion mean PSE and lesion size. The mean PSE of COVID-19 lesions (3.2 ± 4.9%) was significantly lower than that of the pulmonary parenchyma (5.4 ± 3.9%). No significant difference was found among different lesion types. CONCLUSION: OE-UTE-MRI could serve as a promising method for the assessment of lung function or treatment management of COVID-19 patients.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/physiopathology , Lung/diagnostic imaging , Magnetic Resonance Imaging/methods , Pulmonary Ventilation , Adolescent , Adult , Aged , Feasibility Studies , Female , Humans , Imaging, Three-Dimensional , Lung/physiopathology , Male , Middle Aged , Oxygen , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed , Young Adult
14.
J Mol Struct ; 1228: 129435, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1065486

ABSTRACT

In this study, we present the synthesis of novel pyridazin-3(2H)-one derivative namely (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (MBSP). The chemical structure of MBSP was characterized using spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR, UV-Vis, ESI-MS, and finally, the structure was confirmed by single X-ray diffraction studies. The DFT calculation was performed to compare the gas-phase geometry of the title compound to the solid-phase structure of the title compound. Furthermore, a comparative study between theoretical UV-Vis, IR, 1H- and 13C NMR spectra of the studied compound and experimental ones have been carried out. The thermal behavior and stability of the compound were analyzed by using TGA and DTA techniques which revealed that the compound is thermostable up to its melting point. Finally, the in silico docking and ADME studies are performed to investigate whether MBSP is a potential therapeutic for COVID-19.

15.
J Neurol Sci ; 421: 117308, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1033825

ABSTRACT

We evaluated the incidence, distribution, and histopathologic correlates of microvascular brain lesions in patients with severe COVID-19. Sixteen consecutive patients admitted to the intensive care unit with severe COVID-19 undergoing brain MRI for evaluation of coma or neurologic deficits were retrospectively identified. Eleven patients had punctate susceptibility-weighted imaging (SWI) lesions in the subcortical and deep white matter, eight patients had >10 SWI lesions, and four patients had lesions involving the corpus callosum. The distribution of SWI lesions was similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions. Collectively, these radiologic and histopathologic findings add to growing evidence that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.


Subject(s)
Brain Injuries/diagnostic imaging , COVID-19/diagnostic imaging , Magnetic Resonance Imaging/methods , Microvessels/diagnostic imaging , Severity of Illness Index , Brain/blood supply , Brain/diagnostic imaging , Brain Injuries/etiology , COVID-19/complications , Humans , Intensive Care Units/trends , Male , Microvessels/injuries , Middle Aged , Retrospective Studies
16.
Am J Case Rep ; 22: e927011, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1005105

ABSTRACT

BACKGROUND Pandemic coronavirus disease 2019 (COVID-19) originated in Wuhan, China, and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe respiratory symptoms are a hallmark of the disease, which may also include complications related to a hypercoagulable state and central nervous system involvement. These complications can occur during either the acute or the recovery phase. The cerebral involvement typically manifests as intracranial hypertension, intracerebral hemorrhage, diffuse encephalopathy, or cerebral venous thrombosis. The hemorrhagic form of cerebral venous thrombosis can be a diagnostic challenge and is treated by anticoagulation therapy, despite the existence of an intracerebral hemorrhage. This report describes a case of superficial cerebral venous thrombosis and intracerebral hematoma in a 48-year-old man weeks after recovering from the acute phase of SARSCoV-2 infection. CASE REPORT A 48-year-old man with a past medical history of SARS-CoV-2 infection confirmed by SARS-CoV-2 reverse-transcription polymerase chain reaction presented with left upper-limb numbness, weakness, and impaired positional sensorium. After initial stabilization, noncontrast computerized tomography and magnetic resonance imaging confirmed an intracerebral hemorrhage with underlying cerebral venous thrombosis. The patient was successfully treated with enoxaparin anticoagulation therapy, and symptoms improved over the following 12 days. CONCLUSIONS Central nervous system venous thrombosis is an atypical presentation of the hypercoagulable state primarily seen in younger patients, and it can occur in a delayed fashion after recovery from mild forms of COVID-19.


Subject(s)
COVID-19/complications , Cerebral Hemorrhage/diagnostic imaging , Hematoma/diagnostic imaging , Intracranial Thrombosis/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Anticoagulants/therapeutic use , Cerebral Hemorrhage/virology , Enoxaparin/therapeutic use , Hematoma/virology , Humans , Intracranial Thrombosis/drug therapy , Intracranial Thrombosis/virology , Magnetic Resonance Imaging , Male , Middle Aged , Tomography, X-Ray Computed , Venous Thrombosis/drug therapy , Venous Thrombosis/virology
17.
Saudi J Biol Sci ; 28(1): 1100-1108, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-919519

ABSTRACT

The severe acute respiratory syndrome coronavirus, identified as SARS-CoV-2, initially established in Wuhan, China at the end of 2019, affects respiratory infections known as COVID-19. In an extraordinary manner, COVID-19 is affecting human life and has transformed a global public health issue into a crisis. Natural products are already recognized owing to the massive advantageous window and efficient antioxidant, antiviral immunomodulatory, and anti-inflammatory belongings. Additionally, the object of the present study was to demonstrate the inhibitory potential of the natural products coumarins and its analogues alongside SARS coronavirus. The present work, focuses on the synthesis of new coumarin analogues and characterized by FT-IR, 1H and 13C NMR, elemental analyses, and mass spectra. The recently synthesised compounds were projected conceptual association for COVID-19 protease and also to explore in anticipation if this protein will help target protease inhibitor drugs such as Calanolide A, Cardatolide A, Collinin, Inophyllum A, Mesuol, Isomesuol, Pteryxin, Rutamarin, Seselin and Suksdorin. The natural coumarin analogues docking scores were compared to standard Hydroxychloroquine. While the 3D module of SARS coronavirus main protease was predicted with the SWISS MODEL web server, as well as biochemical interaction tests were performed with the AutoDock Vina tool between the target protein with ligands. This research further showed that all the protease inhibitors accessed the target protein with negative dock energy. Molecular docking studies found that the natural coumarin analogue Inophyllum A showed an exceptional potential for inhibition with a binding energy of -8.4 kcal/mol. The synthetic coumarin analogues 1m and 1p both demonstrated a similar binding energy, inhibition potential of -7.9 kcal / mol as opposed to hydroxychloroquine and co-crystallized ligand alpha-ketoamide with binding energy values of -5.8 and -6.6 kcal / mol. All compounds evaluated were known as drug-like in nature, passing Lipinski's "Law of 5" with 0 violations except for alpha-ketoamide, passing Lipinski's "Rule of 5" with 1 violation (MW > 500). The inhibitor binding in silico research thus offers a structural understanding of COVID-19 and molecular interactions across the known protease inhibitors centred on the findings of the multiple sequence alliance.

18.
Nucleic Acids Res ; 48(22): 12415-12435, 2020 12 16.
Article in English | MEDLINE | ID: covidwho-917705

ABSTRACT

The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5' end, the ribosomal frameshift segment and the 3'-untranslated region (3'-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.


Subject(s)
COVID-19/prevention & control , Magnetic Resonance Spectroscopy/methods , Nucleic Acid Conformation , RNA, Viral/chemistry , SARS-CoV-2/genetics , 3' Untranslated Regions/genetics , Base Sequence , COVID-19/epidemiology , COVID-19/virology , Frameshifting, Ribosomal/genetics , Genome, Viral/genetics , Humans , Models, Molecular , Pandemics , SARS-CoV-2/physiology
19.
Cardiovasc Diagn Ther ; 10(5): 1303-1312, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-914917

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has already became a public health emergency of international concern. COVID-19 related cardiac injury remains largely unclear. METHODS: We retrospectively analyzed demographic, clinical, laboratory and cardiovascular imaging data of all consecutively admitted adult COVID-19 patients in Zhuhai, China from January 17th, 2020 to February 18th, 2020. RESULTS: A total of 93 patients were included in the study. Acute cardiac injury was found in 9 (9.7%) COVID-19 patients with median level of hypersensitive cardiac troponin I (hs-cTnI) to be 0.085 µg/L (IQR 0.027-0.560 µg/L). Compared with patients without cardiac injury, the median age of patients with cardiac injury was significantly older (65.0 vs. 44.0, P<0.05), hypertension was significantly more common (44.4% vs. 14.3%, P<0.05), and the proportion of severe-critical cases were greater (77.8% vs. 17.9%, P<0.05). Patients with cardiac injury were more likely have elevation of N-terminal proBNP (NT-proBNP) in comparison (66.7% vs. 10.0%, P<0.05). There was no significant difference in echocardiographic parameters between patients with and without cardiac injury. Multivariable logistic regression analysis indicated that older age (OR: 1.093, 95% CI: 1.011-1.182) and increased NT-proBNP (OR: 10.979, 95% CI: 2.024-59.555) were independent risk factors for cardiac injury. Cardiac magnetic resonance (CMR) imaging performed on three patients at around one month after they underwent significant hs-cTnI elevation showed that they had underlying cardiovascular comorbidities. CONCLUSIONS: Acute cardiac injury was seen in the minority of hospitalized COVID-19 patients in Zhuhai, China. Older age and increased NT-proBNP were associated with acute cardiac injury. REGISTRATION NUMBER: ChiCTR2000030952.

20.
AJNR Am J Neuroradiol ; 42(1): 37-41, 2021 01.
Article in English | MEDLINE | ID: covidwho-895283

ABSTRACT

Brain multivoxel MR spectroscopic imaging was performed in 3 consecutive patients with coronavirus disease 2019 (COVID-19). These included 1 patient with COVID-19-associated necrotizing leukoencephalopathy, another patient who had a recent pulseless electrical activity cardiac arrest with subtle white matter changes, and a patient without frank encephalopathy or a recent severe hypoxic episode. The MR spectroscopic imaging findings were compared with those of 2 patients with white matter pathology not related to Severe Acute Respiratory Syndrome coronavirus 2 infection and a healthy control subject. The NAA reduction, choline elevation, and glutamate/glutamine elevation found in the patient with COVID-19-associated necrotizing leukoencephalopathy and, to a lesser degree, the patient with COVID-19 postcardiac arrest, follow a similar pattern as seen with the patient with delayed posthypoxic leukoencephalopathy. Lactate elevation was most pronounced in the patient with COVID-19 necrotizing leukoencephalopathy.


Subject(s)
COVID-19/diagnostic imaging , Aged , Humans , Leukoencephalopathies/diagnostic imaging , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , SARS-CoV-2 , White Matter
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