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1.
Emerging Infectious Diseases ; 28(4), 2022.
Article in English | ProQuest Central | ID: covidwho-1834284

ABSTRACT

Patients infected with severe acute respiratory syndrome coronavirus 2 might have bacterial and fungal superinfections develop. We describe a clinical case of coronavirus disease with pulmonary aspergillosis associated with Bordetella hinzii pneumonia in an immunocompetent patient in France. B. hinzii infections are rare in humans and develop secondary to immunosuppression or debilitating diseases.

2.
BioMed Research International ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1832664

ABSTRACT

Protein is the material foundation of living things, and it directly takes part in and runs the process of living things itself. Predicting protein complexes helps us understand the structure and function of complexes, and it is an important foundation for studying how cells work. Genome-wide protein interaction (PPI) data is growing as high-throughput experiments become more common. The aim of this research is that it provides a dual-tree complex wavelet transform which is used to find out about the structure of proteins. It also identifies the secondary structure of protein network. Many computer-based methods for predicting protein complexes have also been developed in the field. Identifying the secondary structure of a protein is very important when you are studying protein characteristics and properties. This is how the protein sequence is added to the distance matrix. The scope of this research is that it can confidently predict certain protein complexes rapidly, which compensates for shortcomings in biological research. The three-dimensional coordinates of C atom are used to do this. According to the texture information in the distance matrix, the matrix is broken down into four levels by the double-tree complex wavelet transform because it has four levels. The subband energy and standard deviation in different directions are taken, and then, the two-dimensional feature vector is used to show the secondary structure features of the protein in a way that is easy to understand. Then, the KNN and SVM classifiers are used to classify the features that were found. Experiments show that a new feature called a dual-tree complex wavelet can improve the texture granularity and directionality of the traditional feature extraction method, which is called secondary structure.

3.
Embase; 2020.
Preprint in English | EMBASE | ID: ppcovidwho-334596

ABSTRACT

The current SARS-CoV-2/COVID-19 pandemic wreaks medical and socioeconomic havoc. Despite the availability of vaccines, cost-effective acute treatment options preventing morbidity and mortality are urgently needed. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2. Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 in therapeutic as well as prophylactic regimens. The herbal infusions exerted antiviral effects comparable to interferon-β and remdesivir but outperformed convalescent sera and interferonα2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perillyl alcohol as antiviral compounds. Global mass spectrometry (MS) analyses performed comparatively in two different cell culture infection models revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of the HMOX-1-inducing compounds sulforaphane and fraxetin. In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including variants of concern such as Alpha, Beta, Delta, and Omicron.

4.
Journal of Chemical Education ; 2021.
Article in English | Scopus | ID: covidwho-1829942

ABSTRACT

In the past few decades, chemistry has evolved to interact with various disciplines to synergistically help tackle global challenges. This, in turn, requires that newer generations of chemistry students are trained to be more flexible in accepting and coordinating new concepts. In this experiment, pineapple was used as a key model to allow for the incorporation of multiple important concepts into the laboratory. Using carotenoid separation as a main goal, column chromatography, UV-vis spectroscopy, thin-layer chromatography, high-performance liquid chromatography, mass spectrometry, and principal component analysis can be included in a cohesive laboratory experiment. On the other hand, these activities were also designed to be modular, thus allowing instructors to add, remove, or modify the contents in a highly customizable manner. This makes it highly versatile and amenable to uncertain situations like unexpected university closure due to COVID-19 related lockdown. Overall, this laboratory experiment serves as a practical example of how chemistry can help solve real-world problems while also allowing high flexibility in teaching management. ©

5.
Molecular Cancer Therapeutics ; 20(12 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1822118

ABSTRACT

Intro: Deregulated protein synthesis is a common trait across solid and hematologic malignancies and an attractive target for cancer therapy. Rocaglates compounds that inhibit eukaryotic initiation factor 4A1 (eIF4A1), the essential DEAD-box RNA helicase that resolves mRNA 5'UTR secondary structures during cap-dependent translation initiation. Rocaglates' unique mechanism of action causes sequence-selective mRNA binding by eIF4A1, clamping the inactive helicase onto the transcript. This suppresses translation globally and affects many oncogenic and pro-survival transcripts in particular. Zotatifin, the first-in class synthetic rocaglate, is currently in Phase I clinical trials for the treatment of solid tumors and as an antiviral against SARS-CoV2. Currently, eIF4A1 and DDX3 are the only reported targets of rocaglate-mediated RNA clamping. Employing unbiased proteomic approaches, we have discovered that rocaglates, thought to act as pure eIF4A/translation inhibitors, extensively remodel the translation machinery and translatome. Additionally, mass-spec interrogation for proteins interacting with specific RNA sequences reveals novel targets of rocaglate-mediated, sequence-specific RNA clamping. Methods: We conducted original mass-spectrometry analyses of translational reprogramming by rocaglates. TMT-pSILAC assessed acute changes in protein production, while MATRIX, which captures high-resolution profiles of the translation machinery, revealed translation factors that drive reprogramming in response to rocaglate exposure. We validated results biochemically, in cellulo, and in vivo using patient-derived xenograft (PDX) mouse models. To probe existing and novel rocaglate RNA-clamping targets, we developed unbiased “clampome” assays - in cellulo protein-RNA-pull downs followed by mass-spec analysis of proteins with increased binding to RNA in the presence of rocaglates. Results: We find rocaglates, including zotatifin, have effects far more complex than simple “translational inhibition” as currently defined. Indeed, translatome analysis by TMT-pSILAC revealed myriad up-regulated proteins that drive hitherto unrecognized cytotoxic mechanisms. The GEF-H1 guanine exchange factor, for example, drives anti-survival RHOA/JNK activation, suggesting novel candidate biomarkers of rocaglate clinical outcomes. Translation-machinery analysis by MATRIX identifed rocaglate-induced dependence on specific translation factors including eEF1ϵ1 that drive remodeling. Novel rocaglate RNA-binding targets revealed by clampome studies remain under detailed evaluation as mediators of drug activities. Discussion: Our original proteome-level interrogation revealed that the complete cellular response to these historical “translation inhibitors” is mediated by comprehensive translational landscape remodeling. Effects on a broader suite of RNA binding proteins than eIF4A1 alone we suggest mediate the potent antitumor activities of these unique compounds, elucidation of which permits development of novel precision approaches to targeted translational deregulation in cancer.

6.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821974

ABSTRACT

Symbiotic interaction between the human body and its microbiota is an important issue of modern biomedicine and personalized medicine. However, little is known on molecular mechanisms of that relationship. Bearing in mind the ubiquitous participation of peptides in biomolecular interactions and regulatory processes we attempted direct search of blood peptides originated from microbial proteins. LC-MS/MS analysis was carried out of blood serum and plasma samples taken from 20 healthy donors on Q Exactive HF-X Hybrid Quadrupole-Orbitrap mass-spectrometer. Sample preparation was carried out based on our previously developed method of peptide desorption from the surface of major blood plasma proteins followed by standard chromatographic steps. Mascot and X! Tandem search engines were used for peptide identification. Human protein sequences were taken from UniProt Knowledgebase and sequences of human microbiota proteins-from NIH Human Microbiome Project (HMP). As a result, out of 13625 identified peptides 912 were unique fragments of microbial precursors, which is 6.69% of the total amount of detected bloodstream peptides. In 30 cases peptide identification was confirmed by mass-spectral study of individual synthetic samples. Absolute quantification by the mass-spectrometric method of multiple reaction monitoring (MRM) confirmed the presence of bacterial peptides in plasma and serum in the range of approximately 0.1 nMol/L to 1 mkMol/L, which is comparable to physiologically significant hormone concentrations in human blood in normal conditions. Analysis of the in silico obtained hydrolyzates of microbiotic proteins showed that significant number of the identified peptides are derived from the precursor proteins as a result of hydrolysis with trypsin, chymotrypsin and pepsin, the main proteases of the gastrointestinal system. 60% of the identified “microbial” peptides are derived from the intestine flora, about 20% - from oral microbiota and 20% fall on the remaining microbiotic communities. Most of the precursor proteins refer to intracellular, cytoplasmic proteins. The isolated fraction of peripheral blood mononuclear cells showed increase secretion of proinflammatory cytokines, colony stimulating factors and chemoattractants as the response to the addition of some of the identified microbiotic peptides. The data obtained serve as a basis for the ongoing study of the functional properties of microbiome derived peptides.

7.
Current Tropical Medicine Reports ; 9(1), 2022.
Article in English | EMBASE | ID: covidwho-1821070

ABSTRACT

Purpose of Review: Cryptococcosis of the central nervous system due to Cryptococcus gattii species complex is a serious mycosis with worldwide distribution but of great importance in the tropics. This article aims to review the progress made in these regions in the knowledge of this disease and its etiological agent. Recent Findings: They can be summarized in the presence in apparently immunocompetent patients of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a hidden risk factor for acquiring C. gattii infection;this finding strengthens the concept that C. gattii is an opportunistic pathogen. A greater knowledge of the clinical and molecular epidemiology of C. gattii infection and of the different environmental niches of this fungus in the tropics. The discovery of a new lineage of C. gattii, VGV, in environmental samples from Africa. Until now, the COVID-19 pandemic has not meant an increase in cryptococcosis cases. Summary: Advances have been made in the identification of risk factors for cryptococcosis due to C. gattii as well as in the knowledge of its etiological agent and its relationship with the environment. Remarkably, there have been no significant achievements in diagnosis and treatment notwithstanding the documented importance.

8.
Environmental Toxicology and Chemistry ; 41(5):1111-1114, 2022.
Article in English | EMBASE | ID: covidwho-1820891
9.
Cells ; 11(9), 2022.
Article in English | EMBASE | ID: covidwho-1818055

ABSTRACT

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton’s jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the antiadsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

10.
Frontiers in Physiology ; 12, 2022.
Article in English | EMBASE | ID: covidwho-1818005

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a major concern in critical care medicine with a high mortality of over 30%. Injury to the lungs is caused not only by underlying pathological conditions such as pneumonia, sepsis, or trauma, but also by ventilator-induced lung injury (VILI) resulting from high positive pressure levels and a high inspiratory oxygen fraction. Apart from mechanical factors that stress the lungs with a specific physical power and cause volutrauma and barotrauma, it is increasingly recognized that lung injury is further aggravated by biological mediators. The COVID-19 pandemic has led to increased interest in the role of the renin-angiotensin system (RAS) in the context of ARDS, as the RAS enzyme angiotensin-converting enzyme 2 serves as the primary cell entry receptor for severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. Even before this pandemic, studies have documented the involvement of the RAS in VILI and its dysregulation in clinical ARDS. In recent years, analytical tools for RAS investigation have made major advances based on the optimized precision and detail of mass spectrometry. Given that many clinical trials with pharmacological interventions in ARDS were negative, RAS-modifying drugs may represent an interesting starting point for novel therapeutic approaches. Results from animal models have highlighted the potential of RAS-modifying drugs to prevent VILI or treat ARDS. While these drugs have beneficial pulmonary effects, the best targets and application forms for intervention still have to be determined to avoid negative effects on the circulation in clinical settings.

11.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816906

ABSTRACT

The ability to control the proliferation and cell death by inhibiting specific target kinase offers the opportunity to apply targeted therapies in the treatment of cancer. It has been found that (S)-valine-thiazole-derived compounds such as NEOS-223 are effective inhibitors of one or more of these kinases. NEOS 223 was developed, synthesized, and tested in the NCI 60 human tumor cell-screening panel demonstrating inhibition of colon (-53%), melanoma (-41%), and breast cancers (-9%). Microsomal clearance was determined in mouse, rat, dog, and human, and analyzed by LC-MS/MS by percent of parent material. IC50 values for CYP inhibition of >10 μM were calculated for 1A2, 2C19, and 3A4 with IC50 values of 4.86, 4.31, and 7.84 μM for 2C9 and 2D6. Microsomal clearance was high in all species with clearance rates ranging from 69-136 mL/min/kg. Plasma protein binding was determined by Rapid Equilibrium Dialysis in mice, rats, dogs, and humans. High plasma protein binding (>70%) was observed across all species. Based on the NCI results several cell lines were assayed in an MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) to determine cell viability in the presence of NEOS-223 resulting in <20% viability in colon, breast, melanoma, pancreatic and prostate human cancer cell lines at a 10 uM concentration. Maximum tolerated dose studies were conducted by both intraperitoneal and oral administration in mice. NEOS-223 delivered up to 80 mg/kg was well tolerated. Minimal or no toxicity was observed in acute and repeat dose animal studies. Pharmacokinetics of oral administration demonstrated adequate systemic exposure at therapeutic levels in mice, rats, and dogs. Preliminary in vivo mouse xenograft studies were performed on colon (COLO 205, HT-29 red FLUC), breast (MDA-Sumathi Chittamuru;Timothy M. Murphy;Sara A. Little;Andrew A. Taylor;Roseanne Wexler;Laxman Desai MB-468), melanoma (M-14), pancreatic (PANC-1), and prostate (PC3) human cancer cells with significant tumor inhibition observed compared to positive control agent groups with twice daily dosing of NEOS-223. In addition, a five-day pilot oral toxicity study in rats with dose range-finding studies and a 28-day repeat dose toxicity study performed in both rats and dogs provided favorable results. NEOS-223 has demonstrated active in vitro activity along with a favorable safety profile. in vivo efficacy resulted in inhibition of growth of multiple cell line. As a novel effective structure possibly targeting multiple kinases and transporters in one hybrid molecule, NEOS-223 may be a preferred monotherapy or combined therapy for multiple cancers. If upon further development, this drug is effective in humans, it would advance clinical practice and could improve current therapy significantly.

12.
Toxins ; 14(4):278, 2022.
Article in English | ProQuest Central | ID: covidwho-1810210

ABSTRACT

Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation;cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

13.
Separations ; 9(4):85, 2022.
Article in English | ProQuest Central | ID: covidwho-1810114

ABSTRACT

With an increasing appreciation for the unique pharmacological properties associated with distinct, individual cannabinoids of Cannabis sativa, there is demand for accurate and reliable quantification for a growing number of them. Although recent methods are based on highly selective chromatography-mass spectrometry technology, most are limited to a few cannabinoids, while relying on unnecessarily sophisticated and expensive ultra-high performance liquid chromatography and tandem mass spectrometry. Here we report an optimised, simple extraction method followed by a reliable and simple high performance liquid chromatography method for separation. The detection is performed using a time-of-flight mass spectrometer that is available in most natural products research laboratories. Due to the simplicity of instrumentation, and the robustness resulting from a high resolution in the chromatography of isobaric cannabinoids, the method is well suited for routine phytocannabinoid analysis for a range of applications. The method was validated in terms of detection and quantification limits, repeatability, and recoveries for a total of 17 cannabinoids: detection limits were in the range 11–520 pg when using a 1 µL sample injection volume, and the recovery percentages ranged from 85% to 108%. The validated method was subsequently applied to determine cannabinoid composition in the inflorescences of several medicinal Cannabis sativa varieties.

14.
Molecules ; 27(8):2495, 2022.
Article in English | ProQuest Central | ID: covidwho-1810037

ABSTRACT

(1) Background: ACE and CPN serum activity correlated with disease severity in an earlier study of 45 hospitalized COVID-19 patients. The serum protein profile was investigated in the same cohort here to shed more light on the involvement of the renin–angiotensin system (RAS). (2) Methods: High-definition mass spectrometry-based protein expression analysis was performed, followed by multivariate statistical and network analyses. (3) Results: The protein profiles of hospitalized patients (HoP) differed significantly from those of convalescent and healthy probands. Surprisingly, HoP samples separated into six groups according to their protein profiles: group (G) 1 represented the youngest and the least afflicted patients, and G6 the oldest and critically ill patients. At least two major pathophysiological schemes were indicated based on differing involvement of the kallikrein-kinin system (KKS), the RAS and complement activation. The serum angiotensinogen concentration increased with disease severity. (4) Conclusions: The important role of the RAS in the response to COVID-19 infection was substantiated, but other pathways such as the KKS, plasminogen activation and complement activation influence the systemic response to the infection.

15.
Microorganisms ; 10(4):824, 2022.
Article in English | ProQuest Central | ID: covidwho-1810032

ABSTRACT

The development of antimalarial drug resistance is an ongoing problem threatening progress towards the elimination of malaria, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the development of new antimalarials with untapped targets and low propensity for resistance. In addition, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-xL is a target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothesised that red blood cell (RBC) BCL-xL is essential for Plasmodium development and tested this hypothesis using six BCL-xL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of Plasmodium falciparum 3D7 parasites in vitro at low micromolar or sub-micromolar concentrations. Western blot analysis of infected cell fractions and immunofluorescence microscopy assays revealed that host BCL-xL is relocated from the RBC cytoplasm to the vicinity of the parasite upon infection. Further, immunoprecipitation of BCL-xL coupled with mass spectrometry analysis identified that BCL-xL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results provide interesting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts.

16.
Foods ; 11(8):1107, 2022.
Article in English | ProQuest Central | ID: covidwho-1809802

ABSTRACT

Moringa oleifera is a tree cultivated originally in northern India, whose ancient use as a medicine has demonstrated its antioxidant and anti-inflammatory properties. Due to its richness in minerals and macronutrients, the antioxidant capacity and the mineral bioaccesibility were assessed. In addition, the chemical composition, amino acid, fatty acid, and mineral content were also evaluated. The performed analysis reported a high content of proteins and low content of lipids in the chemical composition. Regarding the mineral content, Ca and Fe presented high bioaccessibility;K, S, Ca, and Fe being the most concentrated elements. The obtained values using FRAP, ABTS, and ORAC methods showed high antioxidant capacity, directly related to the increased content of phenolic compounds. In view of the results, Moringa oleifera can be incorporated into the diet as a functional ingredient or as a fortifier of any kind of food. The important source of minerals, phenolics, proteins, unsaturated fats, and folates make it an excellent extract with beneficial properties.

17.
J Breath Res ; 2022.
Article in English | PubMed | ID: covidwho-1806207

ABSTRACT

COVID-19 detection currently relies on testing by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing. However, SARS-CoV-2 is expected to cause significant metabolic changes in infected subjects due to both metabolic requirements for rapid viral replication and host immune responses. Analysis of volatile organic compounds (VOCs) from human breath can detect these metabolic changes and is therefore an alternative to RT-PCR or antigen assays. To identify VOC biomarkers of COVID-19, exhaled breath samples were collected from two sample groups into Tedlar bags: negative COVID-19 (n=12) and positive COVID-19 symptomatic (n=14). Next, VOCs were analyzed by headspace solid phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME GC-MS). Subjects with COVID-19 displayed a larger number of VOCs as well as overall higher total concentration of VOCs (p < 0.05). Univariate analyses of qualified endogenous VOCs showed approximately 18% of the VOCs were significantly differentially expressed between the two classes (p < 0.05), with most VOCs upregulated. Machine learning multivariate classification algorithms distinguished COVID-19 subjects with over 95% accuracy. The COVID-19 positive subjects could be differentiated into two distinct subgroups by machine learning classification, but these did not correspond with significant differences in number of symptoms. Next, samples were collected from subjects who had previously donated breath bags while experiencing COVID-19, and subsequently recovered (COVID Recovered subjects (n = 11)). Univariate and multivariate results showed > 90% accuracy at identifying these new samples as Control (COVID-19 negative), thereby validating the classification model and demonstrating VOCs dysregulated by COVID are restored to baseline levels upon recovery.

18.
Cell Reports ; 39(4):110744, 2022.
Article in English | ScienceDirect | ID: covidwho-1803707

ABSTRACT

Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic, which has led to a devastating global health crisis. The emergence of variants that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology. Using a comprehensive identification of RNA-binding proteins (RBPs) by mass spectrometry (ChIRP-MS) approach, we identify 107 high-confidence cellular factors that interact with the SARS-CoV-2 genome during infection. By systematically knocking down their expression in human lung epithelial cells, we find that the majority of the identified RBPs are SARS-CoV-2 proviral factors. In particular, we show that HNRNPA2B1, ILF3, QKI, and SFPQ interact with the SARS-CoV-2 genome and promote viral RNA amplification. Our study provides valuable resources for future investigations into the mechanisms of SARS-CoV-2 replication and the identification of host-centered antiviral therapies.

19.
Angewandte Chemie ; 134(19), 2022.
Article in English | ProQuest Central | ID: covidwho-1802056

ABSTRACT

Im Laufe der COVID‐19 Pandemie haben mRNA‐basierte Impfstoffe an immenser Bedeutung gewonnen. Massenspektrometrie ist für die Entwicklung und Analyse von modifizierten RNA Molekülen unerlässlich, setzt jedoch ein grundlegendes Verständnis über Fragmentierungsprozesse voraus. Analog zu der Zersetzung von RNA in Lösung durch Autohydrolyse, kann die Spaltung des RNA Rückgrats ebenso in der Gasphase stattfinden. Bislang sind die Fragmentierungsmechanismen jedoch unzureichend untersucht. In dieser Arbeit wurden Intermediate aus isolierten RNA Dinukleotiden in der Gasphase generiert und mittels kryogener Infrarotspektroskopie in Helium‐Nanotröpfchen untersucht. Die experimentellen Daten, unterstützt durch Dichtefunktionaltheorie, liefern Hinweise dafür, dass die Bildung eines fünfgliedrigen zyklischen Phosphat‐Intermediats begünstigt ist, während lineare oder sechsgliedrige Strukturen ausgeschlossen werden können. Weiterhin zeigen die Experimente, dass eine zusätzliche, bekannte Reaktion von RNA Nukleotiden in Lösung auch in der Gasphase induziert werden kann: die Tautomerisierung von Cytosin. Die beiden beobachteten Reaktionen spiegeln daher universelle und intrinsische Eigenschaften der untersuchten Moleküle wider.

20.
Environmental Pollution ; : 119308, 2022.
Article in English | ScienceDirect | ID: covidwho-1796874

ABSTRACT

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography–mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC–MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

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