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1.
J Cardiovasc Magn Reson ; 24(1): 15, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1731532

ABSTRACT

Most cardiac imaging conferences have adopted social media as a means of disseminating conference highlights to a global audience well beyond the confines of the conference location. A deliberate and thoughtful social media campaign has the potential to increase the reach of the conference and allow for augmented engagement. The coronavirus disease 2019 (COVID-19) pandemic triggered a radical transformation in not just the delivery of healthcare but also the dissemination of science within the medical community. In the past, in-person medical conferences were an integral annual tradition for most medical professionals to stay up to date with the latest in the field. Social distancing requirements of the COVID-19 pandemic resulted in either cancelling medical conferences or shifting to a virtual format. Following suit, for the first time in its history, the 2021 Society for Cardiovascular Magnetic Resonance (SCMR) annual meeting was an all-virtual event. This called for a modified social media strategy which aimed to re-create the sociability of an in-person conference whilst also promoting global dissemination of the science being presented. This paper describes the employment of social media as well as the evolution through the SCMR scientific sessions for 2020 and 2021 that serves as a model for future cardiovascular conferences.


Subject(s)
COVID-19 , Social Media , Humans , Magnetic Resonance Spectroscopy , Pandemics , Predictive Value of Tests , SARS-CoV-2
2.
J Nat Prod ; 85(2): 327-336, 2022 02 25.
Article in English | MEDLINE | ID: covidwho-1655431

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1-4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Microbial Sensitivity Tests/methods , Phloroglucinol/pharmacology , SARS-CoV-2/drug effects , Terpenes/pharmacology , Chromatography, High Pressure Liquid , Chromatography, Liquid , Crystallography, X-Ray , Drug Delivery Systems , Dryopteris/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Docking Simulation , Molecular Structure , Virtual Reality
3.
J Nat Prod ; 84(8): 2385-2389, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1634670

ABSTRACT

The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (1-4), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic cadinane sesquiterpenoids inhibited the SARS-CoV-2 spike-ACE2 interaction, with IC50 values ranging from 64.5 to 99.1 µM. A molecular docking study showed the disruption of the interaction of compound 1 via hydrogen interactions with Arg403, Asp405, and Arg408 of SARS-CoV-2 RBD and Arg393 and His34 residues of ACE2. These results suggested that aromatic cadinane sesquiterpenoids might be useful in developing agents for COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fruiting Bodies, Fungal/chemistry , Phellinus/chemistry , Polycyclic Sesquiterpenes/chemistry , Polycyclic Sesquiterpenes/pharmacology , SARS-CoV-2/drug effects , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Humans , Hydrogen Bonding/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Docking Simulation
4.
Int J Mol Sci ; 23(3)2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1625435

ABSTRACT

Spike protein of SARS-CoV-2 contains a single-span transmembrane (TM) domain and plays roles in receptor binding, viral attachment and viral entry to the host cells. The TM domain of spike protein is critical for viral infectivity. Herein, the TM domain of spike protein of SARS-CoV-2 was reconstituted in detergent micelles and subjected to structural analysis using solution NMR spectroscopy. The results demonstrate that the TM domain of the protein forms a helical structure in detergent micelles. An unstructured linker is identified between the TM helix and heptapeptide repeat 2 region. The linker is due to the proline residue at position 1213. Side chains of the three tryptophan residues preceding to and within the TM helix important for the function of S-protein might adopt multiple conformations which may be critical for their function. The side chain of W1212 was shown to be exposed to solvent and the side chains of residues W1214 and W1217 are buried in micelles. Relaxation study shows that the TM helix is rigid in solution while several residues have exchanges. The secondary structure and dynamics of the TM domain in this study provide insights into the function of the TM domain of spike protein.


Subject(s)
Detergents/pharmacology , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Sequence , COVID-19/virology , Cell Membrane/metabolism , Cross-Linking Reagents/pharmacology , Detergents/chemistry , Humans , Magnetic Resonance Spectroscopy , Micelles , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Protein Domains/drug effects , Protein Structure, Secondary/drug effects , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/drug effects , Spike Glycoprotein, Coronavirus/metabolism
5.
Chem Biodivers ; 18(11): e2100674, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1615945

ABSTRACT

Chemical investigation on a Streptomyces sp. strain MS180069 isolated from a sediment sample collected from the South China Sea, yielded the new benzo[f]isoindole-dione alkaloid, bhimamycin J (1). The structure was determined by extensive spectroscopic analysis, including HRMS, 1D, 2D NMR, and X-ray diffraction techniques. A molecular docking study revealed 1 as a new molecular motif that binds with human angiotensin converting enzyme2 (ACE2), recently described as the cell surface receptor responsible for uptake of 2019-CoV-2. Using enzyme assays we confirm that 1 inhibits human ACE2 79.7 % at 25 µg/mL.


Subject(s)
Alkaloids/chemistry , Geologic Sediments/microbiology , Isoindoles/chemistry , Streptomyces/chemistry , Alkaloids/metabolism , Alkaloids/pharmacology , Alkaloids/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Isoindoles/isolation & purification , Isoindoles/metabolism , Isoindoles/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Docking Simulation , SARS-CoV-2/isolation & purification , Streptomyces/isolation & purification , Streptomyces/metabolism
6.
Chem Biodivers ; 19(1): e202100668, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611203

ABSTRACT

Forsyqinlingines C (1) and D (2), two C9 -monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9 -monoterpenoid alkaloids showed anti-inflammatory activity performed by the inhibitory effect on the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).


Subject(s)
Alkaloids/chemistry , Anti-Inflammatory Agents/chemistry , Antiviral Agents/chemistry , Forsythia/chemistry , Monoterpenes/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Forsythia/metabolism , Fruit/chemistry , Fruit/metabolism , Glucuronidase/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Magnetic Resonance Spectroscopy , Molecular Conformation , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/metabolism , Platelet Activating Factor/pharmacology , Rats , Respiratory Syncytial Viruses/drug effects
8.
Anal Chem ; 94(2): 1333-1341, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1606902

ABSTRACT

Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interfering resonances from lipoprotein lipids themselves. We present a J-Edited DIffusional (JEDI) proton NMR spectroscopic approach to selectively augment signals from the inflammatory marker peaks Glyc and SPCs in blood serum NMR spectra, which enables direct integration of peaks associated with molecules found in specific compartments. We explore a range of pulse sequences that allow editing based on peak J-modulation, translational diffusion, and T2 relaxation time and validate them for untreated blood serum samples from SARS-CoV-2 infected patients (n = 116) as well as samples from healthy controls and pregnant women with physiological inflammation and hyperlipidemia (n = 631). The data show that JEDI is an improved approach to selectively investigate inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.


Subject(s)
COVID-19 , Protons , Biomarkers , Female , Glycoproteins , Humans , Inflammation , Magnetic Resonance Spectroscopy , Phospholipids , Pregnancy , SARS-CoV-2 , Serum
9.
J Cardiovasc Magn Reson ; 23(1): 140, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1590893

ABSTRACT

BACKGROUND: Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort. METHODS AND RESULTS: Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0-13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19-47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87-23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18-21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction. CONCLUSION: No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage. CLINICAL TRIAL REGISTRATION: The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.


Subject(s)
COVID-19 , Myocarditis , COVID-19/complications , Child , Contrast Media , Gadolinium , Humans , Magnetic Resonance Spectroscopy , Myocarditis/diagnostic imaging , Myocarditis/epidemiology , Predictive Value of Tests , Registries , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
10.
Chemphyschem ; 23(4): e202100704, 2022 02 16.
Article in English | MEDLINE | ID: covidwho-1589144

ABSTRACT

Hadamard encoded saturation transfer can significantly improve the efficiency of NOE-based NMR correlations from labile protons in proteins, glycans and RNAs, increasing the sensitivity of cross-peaks by an order of magnitude and shortening experimental times by ≥100-fold. These schemes, however, fail when tackling correlations within a pool of labile protons - for instance imino-imino correlations in RNAs or amide-amide correlations in proteins. Here we analyze the origin of the artifacts appearing in these experiments and propose a way to obtain artifact-free correlations both within the labile pool as well as between labile and non-labile 1 Hs, while still enjoying the gains arising from Hadamard encoding and solvent repolarizations. The principles required for implementing what we define as the extended Hadamard scheme are derived, and its clean, artifact-free, sensitivity-enhancing performance is demonstrated on RNA fragments derived from the SARS-CoV-2 genome. Sensitivity gains per unit time approaching an order of magnitude are then achieved in both imino-imino and imino-amino/aromatic protons 2D correlations; similar artifact-free sensitivity gains can be observed when carrying out extended Hadamard encodings of 3D NOESY/HSQC-type experiments. The resulting spectra reveal significantly more correlations than their conventionally acquired counterparts, which can support the spectral assignment and secondary structure determination of structured RNA elements.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Magnetic Resonance Spectroscopy/methods , Proteins/chemistry , RNA
11.
Carbohydr Polym ; 280: 119006, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1588175

ABSTRACT

Caulerpa lentillifera (Bryopsidophyceae, Chlorophyta) is an edible seaweed attracting great attention for its expansion of farming scale and increasing consumption in these years. In the present study, a sulfated polysaccharide (CLSP-2) was isolated and separated from C. lentillifera, and its chemical structure was elucidated by a series of chemical and spectroscopic methods. Among these methods, mild acid hydrolysis and photocatalytic degradation were applied to release mono- and oligo-saccharide fragments which were further identified by HPLC-MSn analysis, affording the information of the sugar sequences and the sulfate substitution in CLSP-2. Results indicated that the backbone of CLSP-2 was constructed of →6)-ß-Manp-(1→ with sulfated branches at C2, which were comprised of prevalent →3)-ß-Galp4S-(1→, →3)-ß-Galp2,4S-(1→, and minor Xyl. In addition, the virus neutralization assay revealed that CLSP-2 could effectively protect HeLa cells against SARS-CoV-2 infection with an IC50 of 48.48 µg/mL. Hence, the present study suggests CLSP-2 as a promising agent against SARS-CoV-2.


Subject(s)
COVID-19/virology , Caulerpa/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Chromatography, High Pressure Liquid/methods , HeLa Cells , Humans , Hydrolysis , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Molecular Weight , Polysaccharides/analysis , SARS-CoV-2 , Seaweed/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Sulfates/chemistry
13.
PLoS One ; 16(12): e0251834, 2021.
Article in English | MEDLINE | ID: covidwho-1556859

ABSTRACT

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the 1H, 13C and 15N resonance backbone assignment as well as the Cß of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions.


Subject(s)
Magnetic Resonance Spectroscopy/methods , SARS-CoV-2/metabolism , Viral Nonstructural Proteins/chemistry , Amino Acid Sequence , COVID-19/pathology , COVID-19/virology , Carbon-13 Magnetic Resonance Spectroscopy , Humans , Mutation , Nitrogen Isotopes/chemistry , Protein Structure, Secondary , Proton Magnetic Resonance Spectroscopy , SARS-CoV-2/isolation & purification , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism
15.
J Am Chem Soc ; 143(46): 19306-19310, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1510556

ABSTRACT

The 68-kDa homodimeric 3C-like protease of SARS-CoV-2, Mpro (3CLpro/Nsp5), is a promising antiviral drug target. We evaluate the concordance of models generated by the newly introduced AlphaFold2 structure prediction program with residual dipolar couplings (RDCs) measured in solution for 15N-1HN and 13C'-1HN atom pairs. The latter were measured using a new, highly precise TROSY-AntiTROSY Encoded RDC (TATER) experiment. Three sets of AlphaFold2 models were evaluated: (1) MproAF, generated using the standard AlphaFold2 input structural database; (2) MproAFD, where the AlphaFold2 implementation was modified to exclude all candidate template X-ray structures deposited after Jan 1, 2020; and (3) MproAFS, which excluded all structures homologous to coronaviral Mpro. Close agreement between all three sets of AlphaFold models and experimental RDC data is found for most of the protein. For residues in well-defined secondary structure, the agreement decreases somewhat upon Amber relaxation. For these regions, MproAF agreement exceeds that of most high-resolution X-ray structures. Residues from domain 2 that comprise elements of both the active site and the homo-dimerization interface fit less well across all structures. These results indicate novel opportunities for combining experimentation with molecular dynamics simulations, where solution RDCs provide highly precise input for QM/MM simulations of substrate binding/reaction trajectories.


Subject(s)
Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray/methods , SARS-CoV-2 , COVID-19 , Catalytic Domain , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Dynamics Simulation , Protein Conformation , Protein Folding , Software , X-Rays
16.
Molecules ; 26(21)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1488675

ABSTRACT

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.


Subject(s)
Benzylidene Compounds/chemistry , Lactones/chemistry , Nucleosides/chemical synthesis , Ribose/analogs & derivatives , Adenine/analogs & derivatives , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/prevention & control , Humans , Lactones/chemical synthesis , Magnetic Resonance Spectroscopy , Models, Molecular , Nucleosides/metabolism , Purine Nucleosides , Ribose/chemical synthesis , Ribose/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Stereoisomerism
17.
Arch Cardiovasc Dis ; 114(12): 781-792, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1487562

ABSTRACT

BACKGROUND: Inducible ischaemia is a strong marker of vascular vulnerability. Knowing the important role of the vascular tropism of COVID-19 to explain its severity, the presence of a prior inducible ischaemia may be a key pathogenetic determinant of COVID-19 severity. AIMS: To investigate the prognostic value of prior inducible ischaemia on stress cardiovascular magnetic resonance (CMR) to predict death in patients hospitalized for COVID-19. METHODS: We retrospectively analysed consecutive patients referred for stress perfusion CMR during 1/1/18-1/1/20 who were later hospitalized for COVID-19. The primary outcome was all-cause death, including in-hospital and post-hospitalization deaths, based on the electronic national death registry. RESULTS: Among the patients referred for stress CMR, 481 were hospitalized for COVID-19 (mean age 68.4±9.6years, 61.3% male) and completed the follow-up (median [interquartile range] 73 [36-101] days). There were 93 (19.3%) all-cause deaths, of which 13.7% occurred in hospital and 5.6% were post-hospitalization deaths. Age, male sex, hypertension, diabetes, known coronary artery disease (CAD), the presence of prior inducible ischaemia, the number of ischaemic segments, the presence of late gadolinium enhancement and left ventricular ejection fraction were significantly associated with all-cause death. In multivariable stepwise Cox regression analysis, age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01-1.07; P=0.023), hypertension (HR: 2.77; 95% CI: 1.71-4.51; P<0.001), diabetes (HR: 1.72; 95% CI: 1.08-2.74; P=0.022), known CAD (HR: 1.78; 95% CI: 1.07-2.94; P=0.025) and prior inducible ischaemia (HR 2.05; 95% CI: 1.27-3.33; P=0.004) were independent predictors of all-cause death. CONCLUSIONS: In COVID-19 patients, prior inducible ischaemia by stress CMR during the 2years preceding the COVID-19 pandemic was independently associated with all-cause death.


Subject(s)
COVID-19 , Aged , Contrast Media , Female , Gadolinium , Hospitalization , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Male , Middle Aged , Pandemics , Perfusion , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Stroke Volume , Ventricular Function, Left
18.
NMR Biomed ; 35(2): e4637, 2022 02.
Article in English | MEDLINE | ID: covidwho-1487509

ABSTRACT

COVID-19 is a systemic infectious disease that may affect many organs, accompanied by a measurable metabolic dysregulation. The disease is also associated with significant mortality, particularly among the elderly, patients with comorbidities, and solid organ transplant recipients. Yet, the largest segment of the patient population is asymptomatic, and most other patients develop mild to moderate symptoms after SARS-CoV-2 infection. Here, we have used NMR metabolomics to characterize plasma samples from a cohort of the abovementioned group of COVID-19 patients (n = 69), between 3 and 10 months after diagnosis, and compared them with a set of reference samples from individuals never infected by the virus (n = 71). Our results indicate that half of the patient population show abnormal metabolism including porphyrin levels and altered lipoprotein profiles six months after the infection, while the other half show little molecular record of the disease. Remarkably, most of these patients are asymptomatic or mild COVID-19 patients, and we hypothesize that this is due to a metabolic reflection of the immune response stress.


Subject(s)
COVID-19/metabolism , Lipidomics , Magnetic Resonance Spectroscopy/methods , Metabolomics , SARS-CoV-2 , COVID-19/immunology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Humans
19.
ESC Heart Fail ; 8(6): 5583-5588, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487462

ABSTRACT

AIMS: Our study aimed to investigate the cardiac involvement with sensitive tissue characterization in non-hospitalized children with coronavirus disease 2019 (COVID-19) infection using cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: We prospectively enrolled children who recovered from mildly symptomatic COVID-19 infection between November 2020 and January 2021. Patients underwent CMR at 1.5 T (Achieva, Philips Healthcare, Best, the Netherlands) including cine images, native T1 and T2 mapping. Healthy children and paediatric patients with biopsy-proven myocarditis served as control groups. We performed CMR in 18 children with a median (25th-75th percentile) age of 12 (10-15) years, 38 (24-47) days after positive PCR test, and compared them with 7 healthy controls [15 (10-19) years] and 9 patients with myocarditis [10 (4-16) years]. The COVID-19 patients reported no cardiac symptoms. None of the COVID-19 patients showed CMR findings consistent with a myocarditis. Three patients (17%) from the COVID-19 cohort presented with minimal pericardial effusion. CMR parameters of COVID-19 patients, including volumetric and strain values as well as T1 and T2 times, were not significantly different from healthy controls, but from myocarditis patients. These had significantly reduced left ventricular (LV) ejection fraction (P = 0.035), LV global longitudinal strain, and left atrial strain values as well as elevated native T1 values compared with COVID-19 patients (P < 0.001, respectively). CONCLUSIONS: There was no evidence of myocardial inflammation, fibrosis, or functional cardiac impairment in the studied cohort of children recently. CMR findings were comparable with those of healthy controls. Pericardial effusion suggests a mild pericarditis in a small subgroup. This is pointing to a minor clinical relevance of myocardial involvement in children after mildly symptomatic COVID-19 infections.


Subject(s)
COVID-19 , Myocarditis , Adolescent , Child , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Myocarditis/diagnosis , Myocarditis/epidemiology , SARS-CoV-2
20.
Adv Biol (Weinh) ; 5(12): e2101113, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487432

ABSTRACT

Following the entry into the host cell, SARS-CoV-2 replication is mediated by the replication transcription complex (RTC) assembled through a number of nonstructural proteins (Nsps). A monomeric form of Nsp9 is particularly important for RTC assembly and function. In the present study, 136 unique nanobodies targeting Nsp9 are generated. Several nanobodies belonging to different B-cell lineages are expressed, purified, and characterized. Results from immunoassays applied to purified Nsp9 and neat saliva from coronavirus disease (COVID-19) patients show that these nanobodies effectively and specifically recognize both recombinant and endogenous Nsp9. Nuclear magnetic resonance analyses supported by molecular dynamics reveal a composite Nsp9 oligomerization pattern and demonstrate that both nanobodies stabilize the tetrameric form of wild-type Nsp9 also identifying the epitopes on the tetrameric assembly. These results can have important implications in the potential use of these nanobodies to combat viral replication.


Subject(s)
COVID-19 , Single-Domain Antibodies , Antiviral Agents , Humans , Magnetic Resonance Spectroscopy , RNA-Binding Proteins , SARS-CoV-2 , Viral Nonstructural Proteins/genetics
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