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1.
Biomol NMR Assign ; 15(2): 287-295, 2021 10.
Article in English | MEDLINE | ID: covidwho-1442183

ABSTRACT

The current COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a worldwide health crisis, necessitating coordinated scientific research and urgent identification of new drug targets for treatment of COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome comprises a single RNA of about 30 kb in length, in which 14 open reading frames (ORFs) have been annotated, and encodes approximately 30 proteins. The first two-thirds of the SARS-CoV-2 genome is made up of two large overlapping open-reading-frames (ORF1a and ORF1b) encoding a replicase polyprotein, which is subsequently cleaved to yield 16 so-called non-structural proteins. The non-structural protein 1 (Nsp1), which is considered to be a major virulence factor, suppresses host immune functions by associating with host ribosomal complexes at the very end of its C-terminus. Furthermore, Nsp1 facilitates initiation of viral RNA translation via an interaction of its N-terminal domain with the 5' untranslated region (UTR) of the viral RNA. Here, we report the near-complete backbone chemical-shift assignments of full-length SARS-CoV-2 Nsp1 (19.8 kDa), which reveal the domain organization, secondary structure and backbone dynamics of Nsp1, and which will be of value to further NMR-based investigations of both the biochemical and physiological functions of Nsp1.


Subject(s)
Nuclear Magnetic Resonance, Biomolecular , SARS-CoV-2 , Viral Nonstructural Proteins/chemistry , Models, Molecular , Protein Domains
3.
Curr Cardiol Rep ; 23(4): 35, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1160063

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to summarize the application of cardiac magnetic resonance (CMR) in the diagnostic and prognostic evaluation of patients with heart failure (HF). RECENT FINDINGS: CMR is an important non-invasive imaging modality in the assessment of ventricular volumes and function and in the analysis of myocardial tissue characteristics. The information derived from CMR provides a comprehensive evaluation of HF. Its unique ability of tissue characterization not only helps to reveal the underlying etiologies of HF but also offers incremental prognostic information. CMR is a useful non-invasive tool for the diagnosis and assessment of prognosis in patients suffering from heart failure.


Subject(s)
Heart Failure , Contrast Media , Heart Failure/diagnostic imaging , Humans , Magnetic Resonance Imaging , Magnetic Resonance Imaging, Cine , Myocardium , Predictive Value of Tests , Prognosis
4.
Biomol NMR Assign ; 15(2): 287-295, 2021 10.
Article in English | MEDLINE | ID: covidwho-1155327

ABSTRACT

The current COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a worldwide health crisis, necessitating coordinated scientific research and urgent identification of new drug targets for treatment of COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome comprises a single RNA of about 30 kb in length, in which 14 open reading frames (ORFs) have been annotated, and encodes approximately 30 proteins. The first two-thirds of the SARS-CoV-2 genome is made up of two large overlapping open-reading-frames (ORF1a and ORF1b) encoding a replicase polyprotein, which is subsequently cleaved to yield 16 so-called non-structural proteins. The non-structural protein 1 (Nsp1), which is considered to be a major virulence factor, suppresses host immune functions by associating with host ribosomal complexes at the very end of its C-terminus. Furthermore, Nsp1 facilitates initiation of viral RNA translation via an interaction of its N-terminal domain with the 5' untranslated region (UTR) of the viral RNA. Here, we report the near-complete backbone chemical-shift assignments of full-length SARS-CoV-2 Nsp1 (19.8 kDa), which reveal the domain organization, secondary structure and backbone dynamics of Nsp1, and which will be of value to further NMR-based investigations of both the biochemical and physiological functions of Nsp1.


Subject(s)
Nuclear Magnetic Resonance, Biomolecular , SARS-CoV-2 , Viral Nonstructural Proteins/chemistry , Models, Molecular , Protein Domains
5.
J Proteome Res ; 19(11): 4428-4441, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-974865

ABSTRACT

Quantitative nuclear magnetic resonance (NMR) spectroscopy of blood plasma is widely used to investigate perturbed metabolic processes in human diseases. The reliability of biochemical data derived from these measurements is dependent on the quality of the sample collection and exact preparation and analysis protocols. Here, we describe systematically, the impact of variations in sample collection and preparation on information recovery from quantitative proton (1H) NMR spectroscopy of human blood plasma and serum. The effects of variation of blood collection tube sizes and preservatives, successive freeze-thaw cycles, sample storage at -80 °C, and short-term storage at 4 and 20 °C on the quantitative lipoprotein and metabolite patterns were investigated. Storage of plasma samples at 4 °C for up to 48 h, freezing at -80 °C and blood sample collection tube choice have few and minor effects on quantitative lipoprotein profiles, and even storage at 4 °C for up to 168 h caused little information loss. In contrast, the impact of heat-treatment (56 °C for 30 min), which has been used for inactivation of SARS-CoV-2 and other viruses, that may be required prior to analytical measurements in low level biosecurity facilities induced marked changes in both lipoprotein and low molecular weight metabolite profiles. It was conclusively demonstrated that this heat inactivation procedure degrades lipoproteins and changes metabolic information in complex ways. Plasma from control individuals and SARS-CoV-2 infected patients are differentially altered resulting in the creation of artifactual pseudo-biomarkers and destruction of real biomarkers to the extent that data from heat-treated samples are largely uninterpretable. We also present several simple blood sample handling recommendations for optimal NMR-based biomarker discovery investigations in SARS CoV-2 studies and general clinical biomarker research.


Subject(s)
Blood Chemical Analysis/standards , Blood Specimen Collection/instrumentation , Coronavirus Infections , Lipoproteins/blood , Magnetic Resonance Spectroscopy/methods , Pandemics , Pneumonia, Viral , Artifacts , COVID-19 , Hot Temperature , Humans , Reproducibility of Results
6.
Biomol NMR Assign ; 14(2): 329-333, 2020 10.
Article in English | MEDLINE | ID: covidwho-774089

ABSTRACT

The ongoing pandemic caused by the Betacoronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) demonstrates the urgent need of coordinated and rapid research towards inhibitors of the COVID-19 lung disease. The covid19-nmr consortium seeks to support drug development by providing publicly accessible NMR data on the viral RNA elements and proteins. The SARS-CoV-2 genome encodes for approximately 30 proteins, among them are the 16 so-called non-structural proteins (Nsps) of the replication/transcription complex. The 217-kDa large Nsp3 spans one polypeptide chain, but comprises multiple independent, yet functionally related domains including the viral papain-like protease. The Nsp3e sub-moiety contains a putative nucleic acid-binding domain (NAB) with so far unknown function and consensus target sequences, which are conceived to be both viral and host RNAs and DNAs, as well as protein-protein interactions. Its NMR-suitable size renders it an attractive object to study, both for understanding the SARS-CoV-2 architecture and drugability besides the classical virus' proteases. We here report the near-complete NMR backbone chemical shifts of the putative Nsp3e NAB that reveal the secondary structure and compactness of the domain, and provide a basis for NMR-based investigations towards understanding and interfering with RNA- and small-molecule-binding by Nsp3e.


Subject(s)
Betacoronavirus/metabolism , Carbon-13 Magnetic Resonance Spectroscopy , Nitrogen Isotopes/chemistry , Nucleic Acids/metabolism , Proton Magnetic Resonance Spectroscopy , Viral Nonstructural Proteins/chemistry , Protein Binding , Protein Domains , SARS-CoV-2
7.
JAMA Neurol ; 2020 Sep 08.
Article in English | MEDLINE | ID: covidwho-746366

ABSTRACT

IMPORTANCE: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional magnetic resonance imaging (MRI) systems operate at high-strength magnetic fields (1.5-3 T) that require strict, access-controlled environments. Limited access to timely neuroimaging remains a key structural barrier to effectively monitor the occurrence and progression of neurological injury in intensive care settings. Recent advances in low-field MRI technology have allowed for the acquisition of clinically meaningful imaging outside of radiology suites and in the presence of ferromagnetic materials at the bedside. OBJECTIVE: To perform an assessment of brain injury in critically ill patients in intensive care unit settings, using a portable, low-field MRI device at the bedside. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, single-center cohort study of 50 patients admitted to the neuroscience or coronavirus disease 2019 (COVID-19) intensive care units at Yale New Haven Hospital in New Haven, Connecticut, from October 30, 2019, to May 20, 2020. Patients were eligible if they presented with neurological injury or alteration, no contraindications for conventional MRI, and a body habitus not exceeding the scanner's 30-cm vertical opening. Diagnosis of COVID-19 was determined by positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction nasopharyngeal swab result. EXPOSURES: Portable MRI in an intensive care unit room. MAIN OUTCOMES AND MEASURES: Demographic, clinical, radiological, and treatment data were collected and analyzed. Brain imaging findings are described. RESULTS: Point-of-care MRI examinations were performed on 50 patients (16 women [32%]; mean [SD] age, 59 [12] years [range, 20-89 years]). Patients presented with ischemic stroke (n = 9), hemorrhagic stroke (n = 12), subarachnoid hemorrhage (n = 2), traumatic brain injury (n = 3), brain tumor (n = 4), and COVID-19 with altered mental status (n = 20). Examinations were acquired at a median of 5 (range, 0-37) days after intensive care unit admission. Diagnostic-grade T1-weighted, T2-weighted, T2 fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences were obtained for 37, 48, 45, and 32 patients, respectively. Neuroimaging findings were detected in 29 of 30 patients who did not have COVID-19 (97%), and 8 of 20 patients with COVID-19 (40%) demonstrated abnormalities. There were no adverse events or complications during deployment of the portable MRI or scanning in an intensive care unit room. CONCLUSIONS AND RELEVANCE: This single-center series of patients with critical illness in an intensive care setting demonstrated the feasibility of low-field, portable MRI. These findings demonstrate the potential role of portable MRI to obtain neuroimaging in complex clinical care settings.

8.
Radiol Case Rep ; 15(9): 1629-1632, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-457535

ABSTRACT

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A global pandemic was declared by the World Health Organization on 11 March 2020. Approximately 30% of infected individuals are asymptomatic. We present the case of a 68-year-old female who underwent outpatient breast magnetic resonance (MR) imaging for assessment of a left breast mass. The study demonstrated abnormal sub-pleural high T2 signal intensity change within in the partially visualised lungs, which showed enhancement following administration of contrast. Concern was raised that the pulmonary changes may represent COVID-19 infection. The patient was urgently contacted and denied any current symptoms but reported suffering mild upper respiratory tract symptoms two weeks earlier. An outpatient chest radiograph demonstrated changes consistent with COVID-19 infection and the patient was treated as COVID-19 positive and advised to self-isolate for 7 days as per Public Health England guidance. Due to increasing breathlessness the patient presented to our emergency department the next day and underwent a CT pulmonary angiogram which demonstrated segmental pulmonary emboli and sub-pleural consolidation in keeping with COVID-19 infection. This represents the first case of COVID-19 identified on breast MR imaging that the authors have seen and highlights the importance of prompt identification and flagging of incidental pulmonary findings to minimise further transmission of the virus in asymptomatic carriers.

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