SARS-CoV-2 and sodium transport: a diabolical strategy.

The Covid 19 pandemic remains a serious public health problem until effective drugs and/or vaccines are available. Can we explain why so many people remain asymptomatic but nevertheless highly contagious explaining the speed with which the pandemic has spread around the world? Can we explain why the acute respiratory distress syndrome (ARDS) appears late but can so quickly have a fatal outcome? In the lung, mucociliary clearance (CMC) and alveolar clearance (CA) depend on the transport of sodium through the plasma membrane of epithelial cells. This transport is mediated by a highly selective sodium channel (Epithelial Sodium Channel = ENaC) which could be a key element in the pulmonary pathophysiology of SARS-CoV-2 infection.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Exosomes/EVs: BIOXOME: A NATURAL LIPOSOME MIMETIC AS DRUG DELIVERY SYSTEM

Background & Aim: Liposomes are spherical-shaped vesicles composed of one or more lipid bilayers. The ability of liposomes to encapsulate hydro- or lipophilic drugs allowed these vesicles to become a useful drug delivery system. Natural cell membranes, such as Bioxome, have newly emerged as new source of materials for molecular delivery systems. Bioxome are biocompatible and GMP-compliant liposome-like membrane that can be produced from more than 200 cell types. Bioxome self-assemble, with in-process self-loading capacity and can be loaded with a variety of therapeutic compounds. Once close to the target tissue, Bioxome naturally fuse with the cell membrane and release the inner compound. Orgenesis is interested in evaluating the potential of Bioxome as new drug delivery system for treatment of several diseases, including skin repair, local tumour or COVID19. Methods, Results & Conclusion(s): Bioxome were obtained from adipose- derived Mesenchymal Stem Cells, with a process of organic- solvent lipid extraction, followed by lyophilization and sonication assemblage. During the sonication process, Bioxome were charged or not with several cargos. Size distribution of empty Bioxome was detected by Particle Size Analyzer (NanoSight). Electron Microscopy (EM) was performed to assess Bioxome morphology. Lipid content was evaluated by electrospray ionization system. Dose response in vitro test on human lung fibroblasts treated or not with Bioxome encapsulating a specific cargo (API) against COVID19 were performed. NanoSight analysis showed that nanoparticle size in Bioxome samples ranged between 170+/-50 nm, with a concentration ranging between 109-1010+/-106 particles/mL. EM clearly showed the double phospholipid layers that composes the Bioxome. Stability study demonstrated that Bioxome are stable in size and concentration up to 90 days at +4Cdegree or even at RT. No change in size between encapsulated Bioxome with small size (~340 Da) cargo vs empty Bioxome was observed up to 30 days storage. Lipidomic analysis approach revealed that the yield of lipids and their composition are satisfactory for a therapeutic product using Bioxome. Lastly, in the in vitro model of COVID19, Bioxome encapsulating API effectively saved cells from death (20x vs untreated cells) and at lower doses of API than these of non-encapsulated cargo (0.005 microM vs 0.1 microM). Bioxome seems to be an excellent candidate for liposome mimetic tool as drug delivery system for targeting specific organs and diseases treatment.Copyright © 2023 International Society for Cell & Gene Therapy

Lipid-dependent assembly and budding of emerging viral pathogens

Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Lipid-enveloped viruses include dangerous pathogens such as coronaviruses (SARSCoV-2, etc.), filoviruses (Ebola virus and Marburg virus) and paramyxoviruses (Nipah virus, Hendra virus, etc.). Despite understanding some of the basics of how these viruses cause disease and enter host cells, not much is known on how these dangerous pathogens interact with host cell lipids to achieve new virion formation. The viral matrix or membrane protein regulates assembly and budding from the host cell membrane, connecting the viral lipid envelope to the viral nucleocapsid. Depending on the virus family, this assembly and budding may occur at the plasma membrane or the ER-Golgi intermediate compartment. This presentation will detail the biophysical and biochemical basis of how these emerging pathogens hijack host lipid membrane and metabolic networks to form new virus particles that undergo release from the host cell. These studies were funded in part by the National Institute of Allergy and Infectious Diseases (R01AI081077, AI158220, AI169896).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Pathogenesis of encephalopathy and delirium: neocortical neuronal membrane potential and action potential firing are changed by coronavirus-associated cytokines

Introduction: Encephalopathy and delirium are common following coronavirus infection [1], and the associated neuroinflammation often results in long-term behavioral and cognitive impairment. Neurovirulent cytokines (NVC) are strongly implicated in the pathogenesis of coronavirus encephalopathy [2]. We hypothesized that characterizing the abnormal signaling in NVC exposed neurons will enable us to identify targets to treat encephalopathy and prevent its downstream effects. Method(s): We incubated primary mouse neocortical cultures in NVC known to be increased in coronavirus encephalopathy (TNF-alpha, IL-1beta, IL-6, IL-12 and IL-15). Using whole-cell patch clamp methods, we tested how neuronal function was impacted by 22-28-h exposure to NVC. Result(s): We found that NVC depolarized the resting membrane potential (RMP), reduced the firing threshold of neocortical neurons, and increased baseline spontaneous action potential (AP) firing. NVC altered the sensitivity (or input-output properties) of single neurons to changes in their microenvironment. Specifically, decreasing external Ca2+ and Mg2+ from physiological to low (1.1-0.2 mM) levels increased evoked AP firing in control, but not following exposure to NVC. AP firing threshold and spontaneous firing rates returned to control levels 1 h after NVC wash-out. However, the RMP and attenuated sensitivity of evoked APs to changes in the microenvironment remained persistently abnormal suggesting two distinct mechanisms were at play. Interestingly, hyperpolarizing the RMP reversed this altered response. Conclusion(s): Sustained exposure to NVC reversibly depolarizes neocortical neuronal RMP, altering excitability and the ability of neurons to respond to microenvironment changes. By characterizing the pathogenesis of the underlying changes in neuronal function in our model of coronavirus encephalopathy we will identify intervenable drug targets.

SARS-CoV-2 USES ENDOSOMAL MEMBRANES TO BUILD REPLICATION ORGANELLES

Background: The health emergency caused by the COVID-19 pandemic has evidenced that the frequency of spillover episodes of viruses infecting bats to other species, including humans, has significantly increased compared to previous decades. Besides SARS-CoV-2, six other human coronaviruses (NL63, 229E, OC43, HKU1, SARS-CoV and MERS-CoV) emerged in the 20th and 21st century, most likely because of cross-species transmission events from bats. While many of these coronaviruses cause mild respiratory infections, MERS-CoV, SARS-CoV and SARS-CoV-2 can cause severe respiratory distress, particularly in immunocompromised individuals. However, unlike SARS-CoV and MERS-CoV, SARS-CoV-2 is highly contagious, very stable, with many person-to-person transmissions, which can occur even before individuals exhibit any symptoms. While vaccines are readily available, the emergence of new SARS-CoV-2 variants along with the increasing incidence of individuals developing long COVID urge to develop antivirals specific to treat COVID-19. To reach this goal, we need to have a working knowledge of the host-SARS-CoV-2 interactions to identify targets for therapeutic intervention. Method(s): Following that rationale, we focused on understanding how SARSCoV- 2 generates replication organelles (ROs). All coronaviruses need to remodel cellular membranes to create these structures to allow the active replication and transcription of their genome. Due to their relevance for virus replication, disabling RO formation represents a promising strategy to fight SARS-CoV-2. However, the biogenesis mechanism, the origin, and type of these replication organelles are still a major focus of debate. To identify the cellular membranes that SARS-CoV-2 uses to generate ROs we used multiple cell lines and primary cells that were evaluated by fluorescence microscopy, genetic engineering, compounds that specifically inhibit cellular processes, and immunoprecipitation assays to validate protein-protein interactions. We also used RT-qPCR to assess viral genome replication. Result(s): SARS-CoV-2 uses the viral protein NSP6 to remodel endosomal membranes juxtaposed to the ER to generate replication organelles. Specifically, the virus depends on Clathrin, COPB1, and Rab5 for efficient SARSCoV- 2 RNA synthesis. Conclusion(s): Uncovering the origins and mechanism(s) by which SARS-CoV-2 assembles ROs opens new avenues to develop strategies to interfere with RO biogenesis and halt virus replication.

Cocrystallizing and Codelivering Complementary Drugs to MultidrugResistant Tuberculosis Bacteria in Perfecting Multidrug Therapy.

Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.

Hypothesis of a potential antiviral drug

The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.

Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Mesenchymal Stem Cells: A Potent Cell Source for COVID-19

Coronaviruses are enveloped positive-stranded RNA viruses that cause mild to acute respiratory illness. Coronaviruses can merge envelope proteins with the host cell membranes and de-liver their genetic material. Coronavirus disease 2019 (COVID-19) is the seventh coronavirus clos-est to the severe acute respiratory syndrome (SARS) in bats that infects humans. COVID-19 at-tacks the respiratory system and stimulates the host inflammatory responses, promotes the recruit-ment of immune cells, and enhances angiotensin-converting enzyme 2 (ACE2) activities. Patients with confirmed COVID-19 have experienced fever, dry cough, headache, dyspnea, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. Inflammation is a common and important factor in the pathogenesis of COVID-19. In recent years, stem cell-based therapies represent a promising therapeutic option against various diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that can self-renew and differentiate into various tissues of mesodermal ori-gin. MSCs can be derived from bone marrow, adipose tissue, and umbilical cord blood. MSCs, with their unique immunomodulatory properties, represent a promising therapeutic alternative against diseases associated with inflammation. Several previous studies have shown that MSCs with a strong safety profile can improve the treatment of patients with COVID-19. The information in this review provides a summary of the prevention and diagnosis of COVID-19. Also, we focus on the current clinical application of MSCs for treatments of patients with COVID-19.Copyright © 2021 Bentham Science Publishers.

ACE2 expression in the brain during development and susceptibility to brain infection by SARS-COV-2.

The COVID-19 pandemic spread around the world due to the enormous transmission of the SARS-CoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.Copyright © 2023, Instituto de Investigaciones Medicas. All rights reserved.

The Emergence of Novel Coronavirus Disease, Global Treatment Update and its Containment Strategies in Overpopulated Countries: A Review

The ongoing pandemic of the novel coronavirus SARS-CoV-2 (COVID-19) has created a major challenge for the public health worldwide. The reported cases indicate that the outbreak is more widespread than initially assumed. Around 18 million people have been infected with 689,000 reported deaths (August 2020;the number is increasing daily);with a high mutation rate, this virus poses an even more serious threat worldwide. The actual source of COVID-19 is still un-clear;even if the initial reports link it to the Chinese seafood wet market in Wuhan, other animals such as birds, snakes, and many small mammals including bats are also linked with this novel coro-navirus. The structure of the COVID-19 shows distinctive proteins among which spike proteins have a pivotal role in host cell attachment and virus-cell membrane fusion in order to facilitate virus infection. Currently, no specific antiviral treatment or vaccine is available. Various drug can-didates, including SARS-CoV and MERS-CoV protease inhibitors, neuraminidase inhibitors, RNA synthesis inhibitors, ACE2 inhibitors and lungs supportive therapy, are under trials. Cell-based therapy also appeared with remarkable treatment possibilities. In this article, we endeavored to succinctly cover the current and available treatment options, including pharmaceuticals, cell-based therapy, and traditional medicine. We also focused on the extent of damages by this novel coron-avirus in India, Pakistan, and Bangladesh;the strategies adopted and the research activities initiat-ed so far by these densely populated countries (neighboring China) are explained in this review.Copyright © 2021 Bentham Science Publishers.

Pathogenesis, Clinical Manifestation, Diagnosis, Pathological Findings, Treatment Options, Preventive Measures, and Risk Factors of COVID-19

Background: COVID-19 is an infectious disease caused by SARS-CoV-2. The disease has hit hard around the globe and is now a pandemic. As of April 01, 2020, a total of 875,560 cases have been reported and the figures are increasing day by day. Currently, there is no treatment or vaccine available for curing COVID-19 and pharmaceutical companies are racing toward the common goal of achieving the cure. Method(s): Scientific databases, including Science direct, Pub med, Elsevier, Scopus, and Nature, were explored. Data has also been accessed from case reports, newspaper reports, internet data, World Health Organisation (WHO) reports, and Centre of Disease Control (CDCs) reports. The US National Library of Medicine, Clinicaltrials.gov, were accessed to get information about the ongoing clinical trials. The literature survey started in the first week of February 2020 and was completed in the first week of April 2020. Additional literature survey was done in the second week of June 2020. Result(s): The epicentre of COVID-19 is Wuhan City, Hubei Province, China. Coronavirus belongs to Order Nidovirale and is subdivided into four groups alpha, beta, gamma, and delta. Coronavirus 229E, NL63, HKU1, MERS-CoV and SARS-CoV are known to infect humans. It is an enveloped, non-segmented positive-sense RNA virus of size 30-32 kb with several structural and accessory proteins. The pathogenesis of COVID-19 involves attachment of Spike (S) protein of SARS-CoV-2 to the angio-tensin-converting enzyme 2(ACE2) receptor present on the host cell membrane. Clinical manifestation of COVID-19 include fever, cough, complicated dyspnoea, pneumonia, etc. Real-time-PCR is a sensi-tive test for the detection of SARS-CoV. Remdesivir, Bevacizumab, Darunavir and cobicistat, lopinavir-ritonavir, Oseltamavir, hydroxychloroquine, Sarilumab, mRNA-1273, Ad5-nCoV are some of the drugs under the clinical phase of the trial. People with A-positive blood group, with comorbidities like diabe-tes, hypertension, chronic pulmonary obstructive disease, substance abuse disorders, immunocom-promised individuals, health care workers, and older adults are at high risk of getting infected with SARS-CoV-2 Conclusion(s): This article gives insight into the occurrence of COVID-19, classification and structure of SARS-CoV-2, pathogenesis, pathological findings, clinical manifestation, diagnosis, potential treatment options and prevention, and people at risk of COVID-19.Copyright © 2021 Bentham Science Publishers.

COVID-19 Pandemic: Current Scenario, Challenges and Future Perspectives

Background: The new public health emergency of COVID-19 caused by a novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which originated in Wuhan, Hubei province, China in December 2019, evolved into a pandemic in no time and is still in progression. The novel virus mainly targets the lower respiratory system, leading to viral pneumonia, with other associated complications of multi organ failure. Discussion(s): The bats, in particular Rhinolophus affinis, is a natural host of SARS-CoV-2 and the virus is considered to have spread to humans through yet controversial intermediate host pangolins. The incubation period ranges from 2-14 days and mode of person-to-person transmission is primari-ly via the direct contact with the infected person or through the droplets generated by the infected person during coughing or sneezing. The initiation of the infection process by SARS-CoV-2 virus is the invasion of lung type II alveolar cells via a receptor protein called angiotensin-converting enzyme 2 (ACE2) present on the cell membrane with glycosylated spike (S) viral protein that medi-ates host cell invasion. The main diagnostic tools employed are molecular methods based on nucleic acid detection engaging real-time quantitative polymerase chain reaction (RT-qPCR) and a new immunoassays based on antibodies IgM/IgG. Conclusion(s): Due to the lack of specific clinically approved anticovid-19 drugs or vaccines that could be used for its prevention or treatment, the current management approach is essentially sup-portive and symptomatic. The precautionary measures like, social distancing, cleaning hands with soap or sanitizers, using disinfectant solutions to decontaminate the surfaces of things and proper ventilation, wearing masks and other protective gears to curb transmission. The knowledge regard-ing COVID-19 therapies is still evolving and collaborative efforts are being put in to discover definitive therapies on different themes in the form of vaccines, repurposing drugs, RNA interfer-ence, docking studies, etc.Copyright © 2021 Bentham Science Publishers.

The Role of Microparticles in Polycystic Ovarian Syndrome. An Updated Review

Microparticles (MPs) are vesicles of less than 1 mum in diameter (submicron vesicles) shed from plasma membranes to cell activation, injury, and apoptosis response. They consisted of membrane proteins and cytosolic material from the cell they originated. These vesicles are vital mediators of pathological and physiological cellular processes. Polycystic ovary syndrome (PCOS) is a regular endocrine, menstrual and metabolic condition that affects 10-15% of females in their reproductive period. Numerous researches have described the association between low-grade chronic inflammation and PCOS;however, the relation is not well understood. Chronic low-grade inflammation is reflected as a risk factor for cardiovascular disease, atherosclerosis, and endothelial dysfunction, and it is linked to abdominal obesity and insulin resistance (IR). MPs may be useful biomarkers for the early detection of cardiovascular disease and thrombosis in PCOS patients. In March 2020, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic, wreaking havoc on healthcare systems worldwide and the global economy. Obesity, diabetes, and cardiovascular disease have all been linked to COVID-19 increased risk of infection. PCOS patients have recently been identified as an underserved and potentially high-risk demographic for COVID-19 problems. This article tried to review and present recent studies that explored the role of microparticles in polycystic ovarian syndrome.Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.

In Silico Modeling of COVID-19 Pandemic Course Differentiation Using the FOD Model

Background: The strange and still unclear scenarios of COVID-19 pandemic development have raised the question about the reason for the observed essential state and personal differences con-cerning the expansion and severity of the infection process. Some custom activities are taken into consid-eration in an attempt to explain the phenomenon. Alcohol in the diet is suggested in this paper as the possible factor which could explain the observed differentiation. It easily penetrates cells modifying their natural internal environment, and independently influences tissues as the toxic agent being the source of acetyl aldehyde. Objective(s): The process in which the cell seems to be the most sensitive to altered environmental conditions is the protein folding;in particular, its portion occurring in the endoplasmic reticulum where freshly synthesized polypeptides fold and then are introduced to the cell membrane influencing its property and in particular its fluidity, which is the critical parameter deciding the virus penetration into the cell. Method(s): The application of a mathematical model, fuzzy oil drop model FOD, expressing the influence of the environment on the protein folding process shows the mechanism of this influence. Result(s): The differences between statistical assessment of epidemy in Europe and the Far East, which may be correlated with alcohol consumption, suggest the influence of diet on the status of epidemy in these regions. Conclusion(s): The protein folding seems to be the process most sensitive to environmental conditions in the cell. The different diet customs, including the use of alcohol, may disturb the folding process, lower-ing as the result the number of proteins needed for cell membrane stability, thus increasing its fluidity and the cell susceptibility to virus penetration. Observations presented in this paper are based on the initial period of pandemic development and have not been intentionally modified to prevent the influence of additional factors, like government activities or virus mutations.Copyright © 2022 Bentham Science Publishers.

Administration of Exogenous Surfactant and Cytosolic Phospholipase A2alpha Inhibitors may Help COVID-19 Infected Patients with Chronic Diseases

Background: Coronavirus-19 (COVID-19) pandemic is a worldwide public health problem causing 347,070 deaths from December 25, 2019, till May 25, 2020. Phospholipids are structural components of mammalian cytoskeleton and cell membranes. Phosphatidylglycerol is an anionic lipid found in mammalian membranes in low amounts (1-2%) of the total phospholipids. Also, phosphatidylglycerol suppresses viral attachment to the plasma membrane and subsequent replication in lung cells. Phosphatidylglycerol depletion caused by over expression of cytosolic phos-pholipase A2alpha induces lipid accumulation in lung alveoli and promotes acute respiratory distress syndrome (ARDS). An exogenous-surfactant replacement has been successfully achieved in ARDS and improved oxygenation and lung mechanics. Inhibition of cytosolic phospholipase A2alpha impairs an early step of COVID-19 replication. Aim(s): The present study was carried out to explain the correlation between the administration of exogenous artificial surfactant as well as cytosolic phospholipase A2alpha inhibitors to improve oxygenation and lung mechanics and inhibit COVID-19 replication. Method(s): Database research was carried out on Medline, Embase, Cochrane Library, country-spe-cific journals, and following-up WHO reports published between December 25, 2019-May 25, 2020. Result(s): Till 25 May 2020, coronavirus cases were 5,307,298, with 347,070 deathsand 2,314,849 recovered cases. According to the WHO reports, most COVID-19 deaths seen are in people who suffered from other chronic diseases characterized by phospholipidosis and phosphatidylglycerol deficiency, including hypertension, liver, heart, and lung diseases and diabetes. Phospholipases A2 (PLA2) catalyze the cleavage of fatty acids esterified at the sn-2 position of glycerophospholipids leading to enhanced inflammation and lung damage. Also, cytosolic phospholipase A2alpha inhibitors may reduce the accumulation of viral proteins and RNA. In addition, administration of exogenous phospholipid surfactant may help COVID-19 infected patients with ARDS to remove inflammatory mediators. Conclusion(s): The present study showed a relation between phosphatidylglycerol deficiency in COVID-19 infected patients with ARDS and/or chronic diseases and their mortality. These findings also showed an important approach for the prevention and treatment of COVID-19 infections by using cytosolic phospholipase A2alpha inhibitors and exogenous administration of a specific phos-pholipid surfactant.Copyright © 2021 Bentham Science Publishers.

Biomimetic cell-derived nanocarriers in cancer research.

Nanoparticles have now long demonstrated capabilities that make them attractive to use in biology and medicine. Some of them, such as lipid nanoparticles (SARS-CoV-2 vaccines) or metallic nanoparticles (contrast agents) are already approved for their use in the clinic. However, considering the constantly growing body of different formulations and the huge research around nanomaterials the number of candidates reaching clinical trials or being commercialized is minimal. The reasons behind being related to the "synthetic" and "foreign" character of their surface. Typically, nanomaterials aiming to develop a function or deliver a cargo locally, fail by showing strong off-target accumulation and generation of adverse responses, which is connected to their strong recognition by immune phagocytes primarily. Therefore, rendering in negligible numbers of nanoparticles developing their intended function. While a wide range of coatings has been applied to avoid certain interactions with the surrounding milieu, the issues remained. Taking advantage of the natural cell membranes, in an approach that resembles a cell transfer, the use of cell-derived surfaces has risen as an alternative to artificial coatings or encapsulation methods. Biomimetic technologies are based on the use of isolated natural components to provide autologous properties to the nanoparticle or cargo being encapsulated, thus, improving their therapeutic behavior. The main goal is to replicate the (bio)-physical properties and functionalities of the source cell and tissue, not only providing a stealthy character to the core but also taking advantage of homotypic properties, that could prove relevant for targeted strategies. Such biomimetic formulations have the potential to overcome the main issues of approaches to provide specific features and identities synthetically. In this review, we provide insight into the challenges of nano-biointerfaces for drug delivery; and the main applications of biomimetic materials derived from specific cell types, focusing on the unique strengths of the fabrication of novel nanotherapeutics in cancer therapy.

Establishment of angiotensin-converting enzyme 2 and cluster of differentiation 147 dual target cell membrane chromatography based on SNAP-tag technology for screening anti severe acute respiratory syndrome coronavirus 2 active components.

Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147 (CD147) receptors based on SNAP-tag technology provides a comprehensive solution for screening multiple components in complex samples acting on the two receptors. The selectivity and applicability of the system were validated with encouraging results. Under the optimized conditions, this method was used to screen for antiviral components in Citrus aurantium extracts. The results showed that 25 µmol /L of the active ingredient could inhibit virus entry into cells. Hesperidin, neohesperidin, nobiletin, and tangeretin were identified as antiviral components. In vitro pseudovirus assays and macromolecular cell membrane chromatography further verified the interaction of these four components with host-virus receptors, showing good effects on some or all of the pseudoviruses and host receptors. In conclusion, the in-line dual-targeted cell membrane chromatography LC-MS system developed in this study can be used for the comprehensive screening of antiviral components in complex samples. It also provides new insight into small-molecule drug-receptor and macromolecular-protein-receptor interactions.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors