Quantitative Serum NMR Spectroscopy Stratifies COVID-19 Patients and Sheds Light on Interfaces of Host Metabolism and the Immune Response with Cytokines and Clinical Parameters.

The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in a large (534 patient samples, 305 controls) outpatient cohort of recently tested PCR-positive patients. The COVID-19 cohort consisted of patients who were predominantly in the initial phase of the disease and mostly exhibited a milder disease course.

Concurrent J-evolving refocusing pulses.

Conventional refocusing pulses are optimised for a single spin without considering any type of coupling. However, despite the fact that most couplings will result in undesired distortions, refocusing in delay-pulse-delay-type sequences with desired heteronuclear coherence transfer might be enhanced considerably by including coupling evolution into pulse design. We provide a proof of principle study for a Hydrogen-Carbon refocusing pulse sandwich with inherent J-evolution following the previously reported ICEBERG-principle with improved performance in terms of refocusing performance and/or overall effective coherence transfer time.

Diffusion and Relaxation Edited Proton NMR Spectroscopy of Plasma Reveals a High-Fidelity Supramolecular Biomarker Signature of SARS-CoV-2 Infection.

We have applied nuclear magnetic resonance spectroscopy based plasma phenotyping to reveal diagnostic molecular signatures of SARS-CoV-2 infection combined diffusional and relaxation editing (DIRE). We compared plasma from healthy age-matched controls ( = 26) with SARS-CoV-2 negative non-hospitalized respiratory patients and hospitalized respiratory patients ( = 23 and 11 respectively) with SARS-CoV-2 rRT-PCR positive respiratory patients ( = 17, with longitudinal sampling time-points). DIRE data were modelled using principal component analysis and orthogonal projections to latent structures discriminant analysis (O-PLS-DA), with statistical cross-validation indices indicating excellent model generalization for the classification of SARS-CoV-2 positivity for all comparator groups (area under the receiver operator characteristic curve = 1).

Comprehensive and High-Throughput Exploration of Chemical Space Using Broadband F NMR-Based Screening.

Fragment-based lead discovery has become a fundamental approach to identify ligands that efficiently interact with disease-relevant targets. Among the numerous screening techniques, fluorine-detected NMR has gained popularity owing to its high sensitivity, robustness, and ease of use. To effectively explore chemical space, a universal NMR experiment, a rationally designed fragment library, and a sample composition optimized for a maximal number of compounds and minimal measurement time are required.

Homonuclear BIRD-decoupled spectra for measuring one-bond couplings with highest resolution: CLIP/CLAP-RESET and constant-time-CLIP/CLAP-RESET.

Heteronuclear one-bond couplings are of interest for various aspects of structural analysis of small organic molecules, including for example the distinction of axial and equatorial protons or the use of RDCs as angular constraints. Such couplings are most easily measured from pure doublets in HSQC-type spectra. Recently, the fully decoupled RESET HSQC experiment was reported and several other so-called pure-shift methods followed that allow for the removal of splittings due to homonuclear scalar interactions in one and two-dimensional NMR.