The Role of Pulmonary Surfactant Phospholipids in Fibrotic Lung Diseases.

Diffuse parenchymal lung diseases (DPLD) or Interstitial lung diseases (ILD) are a heterogeneous group of lung conditions with common characteristics that can progress to fibrosis. Within this group of pneumonias, idiopathic pulmonary fibrosis (IPF) is considered the most common. This disease has no known cause, is devastating and has no cure. Chronic lesion of alveolar type II (ATII) cells represents a key mechanism for the development of IPF. ATII cells are specialized in the biosynthesis and secretion of pulmonary surfactant (PS), a lipid-protein complex that reduces surface tension and minimizes breathing effort. Some differences in PS composition have been reported between patients with idiopathic pulmonary disease and healthy individuals, especially regarding some specific proteins in the PS; however, few reports have been conducted on the lipid components. This review focuses on the mechanisms by which phospholipids (PLs) could be involved in the development of the fibroproliferative response.

The anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids.

The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of the most dominant molecular species of PG, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent antiviral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung and, thus, are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species-Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

Progress in developing synthetic pathways for novel and complex phospholipid species, such as Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs), is essential for expanding the knowledge and availability of rare and uncommon phospholipid species. These structurally complex phospholipid species have recently gained more attention with promising applications, as active pharmaceutical ingredient carriers in multiple COVID-19 vaccines, or biomarkers for numerous lysosomal storage disorders and certain types of cancers. The presented work facilitates the production of a range of structurally diverse Hemi-BMP and BDP products intending to increase the availability and thereby the understanding of the underlying chemistry for these high-valuable compounds. The transphosphatidylation of phosphatidylcholine with a variety of structurally diverse monoacylglycerols and diacylglycerols is proceeded by phospholipase D (PLD) catalysis in a biphasic system. Optimization in regard to enzyme loading (5 U), substrate mole ratio (1:5 mol/mol), temperature (30 degrees C), and aqueous concentration of (18% v/v) afforded the highest conversion for the model transphosphatidylation of phosphatidylcholine with monoolein, yielding 87% in 2 h. The study additionally proposes a reaction mechanism based on molecular simulation, elegantly elaborating the structural constraints (substrate configuration and character of the fatty acid residues) for access to the active site of PLD accordingly for lower yield of BDPs. The successful system designed for the production of high-valuable Hemi-BMP and BDP-analogues demonstrated in this work promises to enhance the understanding of these complex phospholipids, leading to new scientific breakthroughs.

Antiphospholipid antibody (aPL) presence in COVID-19 patients

Objective: In our study, we aimed to show whether there is a relationship between antiphospholipid antibody (aPL) positivity and complications of COVID-19. Material and Methods: Eighty-three patients who were diagnosed with COVID-19 infection and hospitalized in the intensive care unit (ICU) of Bakirkoy Dr. Sadi Konuk Research and Training Hospital were included in our study as the case group and 79 healthy volunteers as the control group. Only patients with a positive Polymerase Chain Reaction (PCR) test were included in the case group. Serum antiphospholipid antibodies (aPL IgM/G), C-Reactive Protein (CRP), ferritin, procalcitonin (PCT), plasma D-Dimer levels, prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were analyzed by routine laboratory methods. Results: Both groups were found statistically similar in terms of gender (X2 test, p=0.236). The mean age of the case group and control group was 60.54..16.86 and 51.47..14.64 years, respectively. When aPL positivity was evaluated between the case and control groups, a statistically remarkable difference was found between the groups (p=0.046). The case group showed an aPL positivity of 7.5% and the control group 1%. The correlation between D-Dimer, PT, INR, aPTT levels, and aPL IgM/G positivity in the case group was significant. Conclusion: Our results revealed that aPL positivity in patients with COVID-19 infection relate to the severity of the disease, independent from age and gender. To confirm the result of this study further studies with participation of larger patient groups from national and international hospitals are required.

Lipid coating technology: A potential solution to address the problem of sticky containers and vanishing drugs

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. © 2021 The Authors. VIEW published by Shanghai Fuji Technology Consulting Co., Ltd, authorized by Professional Community of Experimental Medicine, National Association of Health Industry and Enterprise Management (PCEM) and John Wiley & Sons Australia, Ltd.

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species─Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

Progress in developing synthetic pathways for novel and complex phospholipid species, such as Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs), is essential for expanding the knowledge and availability of rare and uncommon phospholipid species. These structurally complex phospholipid species have recently gained more attention with promising applications, as active pharmaceutical ingredient carriers in multiple COVID-19 vaccines, or biomarkers for numerous lysosomal storage disorders and certain types of cancers. The presented work facilitates the production of a range of structurally diverse Hemi-BMP and BDP products intending to increase the availability and thereby the understanding of the underlying chemistry for these high-valuable compounds. The transphosphatidylation of phosphatidylcholine with a variety of structurally diverse monoacylglycerols and diacylglycerols is proceeded by phospholipase D (PLD) catalysis in a biphasic system. Optimization in regard to enzyme loading (5 U), substrate mole ratio (1:5 mol/mol), temperature (30 °C), and aqueous concentration of (18% v/v) afforded the highest conversion for the model transphosphatidylation of phosphatidylcholine with monoolein, yielding 87% in 2 h. The study additionally proposes a reaction mechanism based on molecular simulation, elegantly elaborating the structural constraints (substrate configuration and character of the fatty acid residues) for access to the active site of PLD accordingly for lower yield of BDPs. The successful system designed for the production of high-valuable Hemi-BMP and BDP-analogues demonstrated in this work promises to enhance the understanding of these complex phospholipids, leading to new scientific breakthroughs. © 2023 American Chemical Society.

Visible-Light-Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload.

Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405-nm-visible-light-activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism-of-action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy-dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.

From Olive Oil Emulsions to COVID-19 Vaccines: Liposomes Came First.

It has been a long journey from Pliny the Elder (23-79 AD) to the FDA approval of the first injectable nanomedicine in 1997. A journey powered by intellectual curiosity, which began with sprinkling olive oil on seawater and culminated in playing around with smears of egg lecithin on microscopic slides. This brief review highlights how a few pairs of gifted hands attached to highly motivated brains have turned a curious discovery made under a microscopic lens into novel nanotherapeutics including liposome-based anti-cancer drugs and potent liposomal vaccines given to millions.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

THE EFFECT OF HEPATOPROTECTORS ON THE STATE OF THE LIVER IN POST COVID-19 PATIENTS

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.

Disinfectant dodecyl dimethyl benzyl ammonium chloride (DDBAC) disrupts gut microbiota, phospholipids, and calcium signaling in honeybees (Apis mellifera) at an environmentally relevant level.

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.

Lipidomics Revealed Plasma Phospholipid Profile Differences between Deceased and Recovered COVID-19 Patients.

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.

Material Design for Next-Generation mRNA Vaccines Using Lipid Nanoparticles

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.

Elucidating the neuropathophysiology of COVID-19 using quantum dot biomimetics of SARS-CoV-2

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

Lipid coating technology: A potential solution to address the problem of sticky containers and vanishing drugs

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.

The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.

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.

Nanomedicines Targeting Respiratory Injuries for Pulmonary Disease Management

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.

Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids.

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.

Plasma Phospholipids: A Promising Simple Biochemical Parameter to Evaluate COVID-19 Infection Severity.

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.