Coronavirus Interplay With Lipid Rafts and Autophagy Unveils Promising Therapeutic Targets DOI Creative Commons
Katia Fecchi, Simona Anticoli, Daniela Peruzzu

et al.

Frontiers in Microbiology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 11, 2020

Coronaviruses are enveloped, single stranded, positive sense RNA viruses, which can infect a variety of animals as well human hosts, causing enteric diseases and common cold, respectively. In humans the infection usually induces mild respiratory but sometimes it could be responsible for more severe syndrome. Nowadays, appearance new, highly pathogenic lethal coronavirus variant, an epidemic in China now pandemic, represents global problem health. Unfortunately, only limited approaches available to treat coronaviruses infections vaccine against this new variant is not yet available. Lipid rafts small, dynamic plasma membrane microdomains enriched cholesterol, glycosphingolipids phospholipids. They play important role cellular functions, including cell signal transduction or regulation autophagy and, because their capacity cluster several pathogen recognition receptors, they represent port entry microbes. Although recent data highlighted importance either lipid life cycle coronaviruses, exact biological mechanisms completely understood questions remain still unanswered. review, we briefly describe characteristic replication at molecular level. particular, will consider involvement replication. We also hint how manipulation may potential therapeutic target investigated treatment infections.

Language: Английский

Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2 DOI Creative Commons
Tia A. Tummino, Veronica V. Rezelj, Benoit Fischer

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6554), P. 541 - 547

Published: June 22, 2021

Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other from screening in field, we became concerned that phospholipidosis was a shared mechanism underlying antiviral activity of many repurposed drugs. For all 23 cationic amphiphilic tested, including hydroxychloroquine, azithromycin, amiodarone, four others already clinical trials, monotonically correlated efficacy. Conversely, active against same targets did not induce were antiviral. Phospholipidosis depends on physicochemical properties does reflect specific target-based activities-rather, it may be considered toxic confound early drug discovery. Early detection could eliminate these artifacts, enabling focus molecules therapeutic potential.

Language: Английский

Citations

188
Low HDL and high triglycerides predict COVID-19 severity DOI Creative Commons
L. Masana, Eudald Correig, Daiana Ibarretxe

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: March 30, 2021

Abstract Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain association with evolution. Observational cross-sectional study including 1411 hospitalized patients and an available standard prior (n: 1305) or hospitalization 297). usefulness serum total, LDL, non-HDL HDL cholesterol predict prognosis (severe vs mild) was analysed. Patients severe evolution had lower higher triglyceride levels before infection. measured also showed that a outcome associated triglycerides. concentrations were correlated ferritin D-dimer but CRP levels. presence atherogenic dyslipidaemia strongly independently worse prognosis. low high strong predictors course disease. should be considered as sensitive marker inflammation COVID-19.

Language: Английский

Citations

173
Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2 DOI Creative Commons
Florence Carrouel, Lúcio Souza Gonçalves, Maria Pia Conte

et al.

Journal of Dental Research, Journal Year: 2020, Volume and Issue: 100(2), P. 124 - 132

Published: Oct. 22, 2020

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play important role in pathogenicity and transmission SARS-CoV-2. identification targeted antiviral mouth rinses reduce salivary viral load would contribute reducing COVID-19 pandemic. While awaiting results significant clinical studies, which date do not exist, commercial availability leads us search among them for reagents that have specific properties with respect challenges facing this target were examined 7 found commercially available listed on ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, oils. Because SARS-CoV-2 enveloped virus, many outer lipid membrane. Moreover, some can act capsid by denaturing proteins. Until now, there has been no scientific evidence recommend anti–SARS-CoV-2 effect control cavity. This critical review indicates current knowledge these likely improve trends status. finding a strong sign encourage research quality protocols are already literature.

Language: Английский

Citations

159
Dissecting lipid metabolism alterations in SARS-CoV-2 DOI Open Access

Ilaria Casari,

Marcello Manfredi, Pat Metharom

et al.

Progress in Lipid Research, Journal Year: 2021, Volume and Issue: 82, P. 101092 - 101092

Published: Feb. 9, 2021

Language: Английский

Citations

107
MetaboAnalystR 4.0: a unified LC-MS workflow for global metabolomics DOI Creative Commons
Zhiqiang Pang, Lei Xu,

Charles Viau

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 1, 2024

Abstract The wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed perform specific tasks LC-MS based Here we introduce MetaboAnalystR 4.0 as a streamlined pipeline covering raw spectra processing, compound identification, statistical analysis, functional interpretation. key features includes auto-optimized feature detection quantification algorithm for LC-MS1 MS2 deconvolution identification data-dependent or data-independent acquisition, more accurate interpretation through integrated spectral annotation. Comprehensive validation studies using obtained from standards mixtures, dilution series clinical samples have shown its excellent performance across range common such peak picking, deconvolution, with good computing efficiency. Together existing analysis utilities, represents significant step toward unified, end-to-end global the open-source R environment.

Language: Английский

Citations

46
Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications DOI Open Access
Eva Kočar, Tadeja Režen, Damjana Rozman

et al.

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2020, Volume and Issue: 1866(2), P. 158849 - 158849

Published: Nov. 4, 2020

Language: Английский

Citations

137
COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm DOI Creative Commons
Wonhwa Lee, June Hong Ahn, Hee Ho Park

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Sept. 3, 2020

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus bacteria, but its association with diminished cholesterol levels in COVID-19 patients unknown. Here, we evaluated SREBP-2 activation peripheral blood mononuclear cells of and verified the function COVID-19. Intriguingly, report first observation C-terminal fragment patients' propose an indicator for determining severity. We confirmed that SREBP-2-induced biosynthesis was suppressed Sestrin-1 PCSK9 expression, while inflammatory responses upregulated ICU patients. Using infectious disease mouse model, inhibitors NF-κB cytokine storms caused viral infection prevented pulmonary damages. These results collectively suggest can serve severity diagnosis therapeutic target preventing storm lung damage severe

Language: Английский

Citations

127
The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response DOI Creative Commons
Philippe Icard,

Hubert Lincet,

Zherui Wu

et al.

Biochimie, Journal Year: 2020, Volume and Issue: 180, P. 169 - 177

Published: Nov. 12, 2020

Language: Английский

Citations

123
Progress and Concept for COVID‐19 Vaccine Development DOI Open Access
Suh‐Chin Wu

Biotechnology Journal, Journal Year: 2020, Volume and Issue: 15(6)

Published: April 18, 2020

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known by provisional name 2019 novel (2019-nCoV), in city Wuhan China's Hubei province 2019–2020 has been causing significant numbers mortality and morbility humans with infection diseases (COVID-19) fever, illness, pneumonia.[1-3] Till April 8, 2020, there have over 1 431 973 confirmed cases globally, leading to at least 82 085 deaths. These SARS-CoV-2 isolates belong Betacoronavirus genus Coronaviradae family which is an enveloped single-stranded RNA virus containing a 30 kb genome 14 open reading frames including four major viral structure proteins: spike (S), membrane (M), envelope (E), nucleocapsid (N) proteins.[4-7] S gene sequences 93.1% nucleotide sequence identity Rhinolophus affinis bat RaTG13, but only less than 75% (SARS-CoV). compared SARS-CoV three additional short insertions N-terminal domain, out five key residues changes receptor-binding motif protein receptor binding domain (RBD).[6, 7] Although both share same human cellular receptor-angiotensin converting enzyme II, appears be more readily transmitted from human.[1, 9] target for COVID-19 vaccine development, mainly based on elicitation neutralizing antibodies as immune correlates protection. current status development includes, i) phase I candidates, ii) 11 preclinical iii) 26 research-stage candidates (Table 1; [https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker?feed=Regulatory-Focus?utm_source=Facebook&utm_medium=social&utm_campaign=Regulatory-Focus]). Most these are antigen either inactivated vaccines, subunit vectored nucleic acid-based DNA or mRNA vaccines. Among Coalition Epidemic Preparedness Innovations (CEPI) provided funding develop vaccines using following platform technology: a) Curevac Inc. (mRNA), b) Inovio Pharmaceuticals (DNA), c) Moderna, d) University Queensland (molecular clam), e) Novavax (nanoparticles), f) Oxford (adenovirus vector), g) Hong Kong (live-attenuated influenza virus), h) Institute Pasteur (measles vector) accelerate enable equitable access people during outbreaks [https://cepi.net/covid-19/]. Phase NCT04283461 ChiCTR2000030906 NCT04336410 Re-purposed SARS vaccine; S1 RBD To date, many previous studies SARS-CoV, Middle East syndrome-related (MERS-CoV), other revealed several safety concerns associated use S-based inflammatory immunopathological effects such pulmonary eosinophilic infiltration antibody-dependent disease enhancement (ADE) subsequent challenge vaccinated animals.[10-21] anti-S ADE may facilitate uptake macrophage expressing FcR, stimulation production proinflammatory cytokines (IL-6, IL-8, MCP1) loss tissue-repaired cytokine (TGFβ).[22] Moreover, Th2-associated immunopathology documented syncytial after challenge[23-25] MERS-CoV challenge.[20] Thus, potentially harmful responses against any coronaviruses should carefully assessed trials.[26] It proposed that epitope-rich region, instead entire full-length alternative development.[27] Whether SARS-CoV-2, selection Th1-skewed adjuvants rather alum adjuvant, can avoid inflammatory, immunopathological, effects, requires further animal models trials. findings particularly important developing safe effective vaccine. Suh-Chin Wu This work was supported Ministry Science Technology, Taiwan (MOST108-2321-B-007-001, MOST108-2321-B-002-006), National Tsing Hua (109R2807E1). author declares no conflict interest.

Language: Английский

Citations

115
Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication DOI Creative Commons
Caroline G. Williams, Alexander S. Jureka, Jesus A. Silvas

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 36(5), P. 109479 - 109479

Published: July 20, 2021

Coronaviruses rely on host membranes for entry, establishment of replication centers, and egress. Compounds targeting cellular membrane biology lipid biosynthetic pathways have previously shown promise as antivirals are actively being pursued treatments other conditions. Here, we test small molecule inhibitors that target the PI3 kinase VPS34 or fatty acid metabolism anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. Our studies determine compounds potent SARS-CoV-2 inhibitors. Mechanistic with multiple steps up- downstream synthase (FASN) identify importance triacylglycerol production protein palmitoylation requirements efficient viral RNA synthesis infectious virus production. Further, FASN knockout results in significantly impaired can be rescued supplementation. Together, these clarify roles promising avenues development countermeasures against SARS-CoV-2.

Language: Английский

Citations

98