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1.
Vestnik Sovremennoi Klinicheskoi Mediciny ; 15(5):22-26, 2022.
Article in Russian | Scopus | ID: covidwho-2145926

ABSTRACT

Introduction. In previous studies, it was found that MERS-CoV and SARS-CoV cause damage to parenchymal organs, including liver damage in patients with COVID-19. Virus-induced influence on hepatocytes and cholangiocytes is considered one of the possible factors of liver failure. Direct viral damage to the liver can be detected in the infectious period, inflammatory and toxic damage can develop both in the acute period and in the post-infectious phase against the background of the rehabilitation period. Aim. The aim of the study was to study the effect of various hepatoprotectors on the functional state of the liver in patients in the early rehabilitation period of COVID-19. Material and methods. 243 post COVID-19 patients were under observation, depending on the therapy, the patients were divided into 4 groups: group 0 – group (n=60) – therapy without hepatoprotectors;ursodeoxycholic acid group (n=61) – ursodeoxycholic acid was included in therapy;glycyrrhizic acid and phospholipids group (n=63) – glycyrrhizic acid and phospholipids in the form of Phosphogliv tablets are included in therapy;group ademeteonin (n=59) – ademeteonin is included in therapy. The control examination was carried out a month later. The control group consisted of 20 healthy individuals. To assess the functional state of the liver in the blood of patients, the enzymes alanine aminotransferase, aspartate aminotransferase, gamma-glutamylaminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin was determined. Conclusion. In patients in the early rehabilitation period of COVID-19, there are increase in the levels of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase and bilirubin in the blood, which indicates functional liver disorders. The use of hepatoprotectors makes it possible to increase the positive effect of rehabilitation on the severity of markers of cytolytic and cholestatic syndromes. Ursodeoxycholic acid has the most pronounced effect on normalization of alanine aminotransferase, total and direct bilirubin levels. © 2022, LLC "IMC" Modern Clinical Medicine. All rights reserved.

2.
Environ Int ; 170: 107639, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2120188

ABSTRACT

One of the impacts of the Coronavirus disease 2019 (COVID-19) pandemic has been a profound increase in the application amounts of disinfectants. Dodecyl dimethyl benzyl ammonium chloride (DDBAC) is a widely used disinfectant, yet its hazards to non-target species remain largely unknown. We are unaware of any studies assessing DDBAC's impacts on honeybee, a pollinator species that is a useful indicator of environmental pollution essential for many forms of agricultural production. Here, we assessed the potentially negative effects of DDBAC on honeybees. After conducting a formal toxicity evaluation of DDBAC on honeybee mortality, we detected an accumulation of DDBAC in the honeybee midgut. We subsequently studied the midgut tissues of honeybees exposed to sub-lethal concentrations of DDBAC: histopathological examination revealed damage to midgut tissue upon DDBAC exposure, microbiome analysis showed a decreased abundance of beneficial midgut microbiota, lipidomics analysis revealed a significant reduction in cell membrane phospholipids with known functions in signal transduction, and a transcriptome analysis detected altered expression of genes involved in calcium signaling pathways (that variously function in calcium absorption, muscle contraction, and neurotransmission). Thus, our study establishes that DDBAC impacts honeybee midgut functions at multiple levels. Our study represents an early warning about the hazards of DDBAC and appeals for the proper stewardship of DDBAC to ensure the protection of our ecological environment.

3.
Biomolecules ; 12(10)2022 10 15.
Article in English | MEDLINE | ID: covidwho-2071207

ABSTRACT

Thorough understanding of metabolic changes, including lipidome alteration, associated with the development of COVID-19 appears to be crucial, as new types of coronaviruses are still reported. In this study, we analyzed the differences in the plasma phospholipid profiles of the deceased COVID-19 patients, those who recovered and healthy people. Due to identified abnormalities in plasma phospholipid profiles, deceased patients were further divided into two subgroups (D1 and D2). Increased levels of phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylserines (PS) were found in the plasma of recovered patients and the majority of deceased patients (first subgroup D1) compared to the control group. However, abundances of all relevant PE, PC and PS species decreased dramatically in the plasma of the second subgroup (D2) of five deceased patients. These patients also had significantly decreased plasma COX-2 activity when compared to the control, in contrast to unchanged and increased COX-2 activity in the plasma of the other deceased patients and recovered patients, respectively. Moreover, these five deceased patients were characterized by abnormally low CRP levels and tremendous increase in LDH levels, which may be the result of other pathophysiological disorders, including disorders of the immune system, liver damage and haemolytic anemia. In addition, an observed trend to decrease the autoantibodies against oxidative modifications of low-density lipoprotein (oLAb) titer in all, especially in deceased patients, indicate systemic oxidative stress and altered immune system that may have prognostic value in COVID-19.


Subject(s)
COVID-19 , Phospholipids , Humans , Phospholipids/metabolism , Phosphatidylethanolamines/metabolism , Lipidomics , Phosphatidylserines/metabolism , Cyclooxygenase 2 , Phosphatidylcholines , Lipoproteins, LDL , Autoantibodies
4.
Polymer Reviews ; 2022.
Article in English | Scopus | ID: covidwho-1984894

ABSTRACT

Vaccine development is among the critical issues for ceasing the COVID-19 pandemic. This review discusses the current usage of biomaterials in vaccine development and provides brief descriptions of the vaccine types and their working mechanisms. New types of vaccine platforms (next-generation vaccines and DNA- or mRNA-based vaccines) are discussed in detail. The mRNA vaccine encoding the spike protein viral antigen can be produced in a cell-free system, suggesting that mRNA vaccines are safer than “classic vaccines” using live or inactivated virus. The mRNA vaccine efficacy is typically high at approximately 95%. However, most mRNA vaccines need to be maintained at −20 or −70 degrees for storage for long periods (half a year) and their transportation because of mRNA vaccine instability in general, although mRNA vaccines with unmodified and self-amplifying RNA (ARCT-154, Arcturus), which have a lyophilized form, have recently been reported to be kept at room temperature. mRNA vaccines are typically entrapped in lipid nanoparticles composed of ionizable lipids, polyethylene glycol (PEG)-lipids, phospholipids, and cholesterol. These components and their composition affect mRNA vaccine stability and efficacy and the size of the mRNA vaccine. The development of an improved mRNA vaccine entrapped in sophisticated biomaterials, such as novel lipid nanoparticles, using new types of biopolymers or lipids is necessary for high efficacy, safe transportation and long-term storage of the next generation of mRNA vaccines under mild conditions. © 2022 Taylor & Francis Group, LLC.

5.
Colloidal Nanoparticles for Biomedical Applications XVII 2022 ; 11977, 2022.
Article in English | Scopus | ID: covidwho-1962038

ABSTRACT

Quantum dots were encapsulated in polymeric phospholipid micelles conjugated to multiple ligands of SARS-CoV-2 spike protein to form fluorescent biomimetic nanoparticles for SARS-CoV-2 (COVID-QDs). Phosphatidylethanolaminepolyethylene glycol (PE:PEG) was appended with bis(4-methylphenyl)sulfone to form PE:PEG:bis-sulfone and self-assembled into micelles around CdSe/CdS core/shell quantum dots via thin-film rehydration. The introduction of the bis-sulfone group the surface of the micelle-encapsulated quantum dots provides multiple sites for conjugation to his-tagged SARS-CoV-2 spike protein via a bisalkylation mechanism. Based on the eluted unconjugated fraction, we estimate that an average of seven spike proteins are conjugated per COVID-QD. We treated an in-vitro model system for the neurovascular unit (NVU) with these COVID-QD constructs to investigate the COVID-QDs, and by proxy SARS-CoV-2, may modulate the NVU leading to the COVID-19 associated neuropathophysiology. © 2022 SPIE

6.
View ; 3(3), 2022.
Article in English | ProQuest Central | ID: covidwho-1870940

ABSTRACT

Pharmaceutical drugs and vaccines require the use of material containers for protection, storage, and transportation. Glass and plastic materials are widely used for packaging, and a longstanding challenge in the field is the nonspecific adsorption of pharmaceutical drugs to container walls – the so‐called “sticky containers, vanishing drugs” problem – that effectively reduces the active drug concentration and can cause drug denaturation. This challenge has been frequently discussed in the case of the anticancer drug, paclitaxel, and the ongoing coronavirus disease 2019 (COVID‐19) pandemic has brought renewed attention to this material science challenge in light of the need to scale up COVID‐19 vaccine production and to secure sufficient quantities of packaging containers. To reduce nonspecific adsorption on inner container walls, various strategies based on siliconization and thin polymer films have been explored, while it would be advantageous to develop mass‐manufacturable, natural material solutions, especially ones involving pharmaceutical grade excipients. Inspired by how lipid nanoparticles have revolutionized the vaccine field, in this perspective, we discuss the prospects for developing lipid bilayer coatings to prevent nonspecific adsorption of pharmaceutical drugs and vaccines and how recent advances in lipid bilayer coating fabrication technologies are poised to accelerate progress in the field. We critically discuss recent examples of how lipid bilayer coatings can prevent nonspecific sticking of proteins and vaccines to relevant material surfaces and examine future translational prospects.

7.
J Lipid Res ; 63(6): 100208, 2022 06.
Article in English | MEDLINE | ID: covidwho-1859914

ABSTRACT

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.


Subject(s)
COVID-19 , Mouthwashes , Antiviral Agents , Cetylpyridinium , Humans , Lipids , Mouthwashes/pharmacology , Povidone-Iodine , RNA, Viral , SARS-CoV-2
8.
Advanced Functional Materials ; 2022.
Article in English | Scopus | ID: covidwho-1729090

ABSTRACT

The respiratory system holds crucial importance in the biology of vertebrate animals. Injuries of the respiratory system caused by viral infections (e.g., by COVID-19, MERS, and SARS) can lead to severe or lethal conditions. So far there are no effective treatments for respiratory injuries. This represents a highly unmet clinical need, e.g., during the current COVID-19 pandemic. Nanomedicines have high potential in the treatment of respiratory injuries. In this review, the pathology and clinical treatments of major respiratory injuries, acute lung injury, and acute respiratory distress syndrome are briefly summarized. The review primarily focuses on nanomedicines based on liposomes, solid lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, which are tested in preclinical models for the treatment of respiratory injuries. These nanomedicines are utilized to deliver a variety of therapeutic agents, including corticosteroids, statins, and nucleic acids. Furthermore, nanomedicines are also investigated for other respiratory diseases including chronic obstructive pulmonary disease and asthma. The promising preclinical results of various nanoformulations from these studies suggest the potential of nanomedicines for future clinical management of respiratory viral infections and diseases. © 2022 The Authors.

9.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(6): 159139, 2022 06.
Article in English | MEDLINE | ID: covidwho-1719329

ABSTRACT

Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of vertebrate lungs. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), are present within the alveoli at very high concentrations, and exert anti-inflammatory effects by regulating multiple Toll like receptors (TLR2/1, TLR4, and TLR2/6) by antagonizing cognate ligand-dependent activation. POPG also attenuates LPS-induced lung injury in vivo. In addition, these lipids bind directly to RSV and influenza A viruses (IAVs) and block interaction between host cells and virions, and thereby prevent viral replication in vitro. POPG and PI also inhibit RSV and IAV infection in vivo, in mice and ferrets. The lipids markedly inhibit SARS-CoV-2 infection in vitro. These findings suggest that both POPG and PI have strong potential to be applied as both prophylaxis and post-infection treatments for problematic respiratory viral infections.


Subject(s)
COVID-19 , Pulmonary Surfactants , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ferrets/metabolism , Lung/metabolism , Mice , Phospholipids/metabolism , Pulmonary Surfactants/metabolism , Pulmonary Surfactants/pharmacology , SARS-CoV-2 , Toll-Like Receptor 2
10.
Bioinform Biol Insights ; 15: 11779322211055891, 2021.
Article in English | MEDLINE | ID: covidwho-1528659

ABSTRACT

BACKGROUND: Coronavirus-19 (COVID-19) pandemic is a worldwide public health problem that has been known in China since December 25, 2019. Phospholipids are structural components of the mammalian cytoskeleton and cell membranes. They suppress viral attachment to the plasma membrane and subsequent replication in lung cells. In the virus-infected lung, phospholipids are highly prone to oxidation by reactive oxygen species, leading to the production of oxidized phospholipids (OxPLs). OBJECTIVE: This study was carried out to explain the correlation between the level of plasma phospholipids in patients with COVID-19 infection and the levels of cytokine storms to assess the severity of the disease. METHODS: Plasma samples from 34 enrolled patients with mild, moderate, and severe COVID-19 infection were collected. Complete blood count (CBC), plasma levels of D-dimer, ferritin, C-reactive protein (CRP), cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), phospholipids, secretory phospholipase A2 (sPLA2)α2, and cytokine storms were estimated, and lung computed tomography (CT) imaging was detected. RESULTS: The CBC picture showed the presence of leukopenia, lymphopenia, and eosinopenia in patients with COVID-19 infection. Furthermore, a significant increase was found in plasma levels of D-dimer, CRP, ferritin, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-13 as well as sPLA2α2 activity compared to normal persons. However, plasma levels of phospholipids decreased in patients with moderate and severe COVID-19 infection, as well as significantly decreased in levels of triacylglycerols and HDL-C in plasma from patients with severe infection only, compared to normal persons. Furthermore, a lung CT scan showed the presence of inflammation in a patient with mild, moderate, and severe COVID-19 infection. CONCLUSIONS: This study shows that there is a correlation between plasma phospholipid depletion and elevated cytokine storm in patients with COVID-19 infection. Depletion of plasma phospholipid levels in patients with COVID-19 infection is due to oxidative stress, induction of cytokine storm, and systemic inflammatory response after endothelial cell damage promote coagulation. According to current knowledge, patients with COVID-19 infection may need to administer surfactant replacement therapy and sPLA2 inhibitors to treat respiratory distress syndrome, which helps them to maintain the interconnected surfactant structures.

11.
J Lipid Res ; 62: 100129, 2021.
Article in English | MEDLINE | ID: covidwho-1440205

ABSTRACT

The significant morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 infection has underscored the need for novel antiviral strategies. Lipids play essential roles in the viral life cycle. The lipid composition of cell membranes can influence viral entry by mediating fusion or affecting receptor conformation. Upon infection, viruses can reprogram cellular metabolism to remodel lipid membranes and fuel the production of new virions. Furthermore, several classes of lipid mediators, including eicosanoids and sphingolipids, can regulate the host immune response to viral infection. Here, we summarize the existing literature on the mechanisms through which these lipid mediators may regulate viral burden in COVID-19. Furthermore, we define the gaps in knowledge and identify the core areas in which lipids offer therapeutic promise for severe acute respiratory syndrome coronavirus 2.


Subject(s)
COVID-19/immunology , Cell Membrane/immunology , Eicosanoids/immunology , SARS-CoV-2/physiology , Sphingolipids/immunology , Virus Replication/immunology , Humans
12.
Front Physiol ; 12: 667024, 2021.
Article in English | MEDLINE | ID: covidwho-1247901

ABSTRACT

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

13.
Prostaglandins Other Lipid Mediat ; 154: 106540, 2021 06.
Article in English | MEDLINE | ID: covidwho-1096205

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is upsetting the world and innovative therapeutic solutions are needed in an attempt to counter this new pandemic. Great hope lies in vaccines, but drugs to cure the infected patient are just as necessary. In the most severe forms of the disease, a cytokine storm with neuroinflammation occurs, putting the patient's life at serious risk, with sometimes long-lasting sequelae. Palmitoylethanolamide (PEA) is known to possess anti-inflammatory and neuroprotective properties, which make it an ideal candidate to be assumed in the earliest stage of the disease. Here, we provide a mini-review on the topic, pointing out phospholipids consumption in COVID-19, the possible development of an antiphospholipid syndrome secondary to SARS-CoV-2 infection, and reporting our preliminary single-case experience concerning to a 45-year-old COVID-19 female patient recently treated with success by micronized / ultramicronized PEA.


Subject(s)
Amides/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Antiphospholipid Syndrome/drug therapy , COVID-19/drug therapy , Ethanolamines/administration & dosage , Neuroprotective Agents/administration & dosage , Palmitic Acids/administration & dosage , SARS-CoV-2/metabolism , Antiphospholipid Syndrome/etiology , Antiphospholipid Syndrome/metabolism , Antiphospholipid Syndrome/pathology , COVID-19/complications , COVID-19/metabolism , COVID-19/pathology , Female , Humans , Middle Aged
16.
Cell Stress Chaperones ; 25(6): 979-991, 2020 11.
Article in English | MEDLINE | ID: covidwho-679678

ABSTRACT

Heat shock proteins (HSPs) are ubiquitous polypeptides expressed in all living organisms that participate in several basic cellular processes, including protein folding, from which their denomination as molecular chaperones originated. There are several HSPs, including HSPA5, also known as 78-kDa glucose-regulated protein (GRP78) or binding immunoglobulin protein (BIP) that is an ER resident involved in the folding of polypeptides during their translocation into this compartment prior to the transition to the Golgi network. HSPA5 is detected on the surface of cells or secreted into the extracellular environment. Surface HSPA5 has been proposed to have various roles, such as receptor-mediated signal transduction, a co-receptor for soluble ligands, as well as a participant in tumor survival, proliferation, and resistance. Recently, surface HSPA5 has been reported to be a potential receptor of some viruses, including the novel SARS-CoV-2. In spite of these observations, the association of HSPA5 within the plasma membrane is still unclear. To gain information about this process, we studied the interaction of HSPA5 with liposomes made of different phospholipids. We found that HSPA5 has a high affinity for negatively charged phospholipids, such as palmitoyl-oleoyl phosphoserine (POPS) and cardiolipin (CL). The N-terminal and C-terminal domains of HSPA5 were independently capable of interacting with negatively charged phospholipids, but to a lesser extent than the full-length protein, suggesting that both domains are required for the maximum insertion into membranes. Interestingly, we found that the interaction of HSPA5 with negatively charged liposomes promotes an oligomerization process via intermolecular disulfide bonds in which the N-terminus end of the protein plays a critical role.


Subject(s)
Heat-Shock Proteins/metabolism , Liposomes/metabolism , Phospholipids/chemistry , Amino Acid Sequence , Betacoronavirus/isolation & purification , Betacoronavirus/metabolism , COVID-19 , Calorimetry , Cardiolipins/chemistry , Cardiolipins/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum Chaperone BiP , HSP70 Heat-Shock Proteins/chemistry , HSP70 Heat-Shock Proteins/metabolism , Heat-Shock Proteins/chemistry , Heat-Shock Proteins/genetics , Humans , Liposomes/chemistry , Pandemics , Phosphatidylserines/chemistry , Phosphatidylserines/metabolism , Phospholipids/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Domains , Protein Multimerization , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , SARS-CoV-2 , Sequence Alignment
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