Immunogenetic landscape of COVID-19 infections related neurological complications

The human leukocyte antigen (HLA) is a critical component of antigen presentation and plays crucial role in conferring differential susceptibility and severity of diseases caused by viruses such as COVID-19. The immunogenetic profile of populations, BCG vaccination status, and a host of lifestyle factors might contribute to the observed variations in mortality rates due to COVID-19. These genetic, epigenetic, and environmental factors could widely influence infection dynamics and immune responses against COVID-19. The aim of this review is to provide an update on HLA association with SARS-CoV-2 infection in global populations and to highlight the possible neurological involvements. We also set out to explore the HLA immunogenetic markers related to COVID‐19 infections that can be used in screening high‐risk individuals for personalized therapies and in community-based vaccine development. © 2023 Elsevier Inc. All rights reserved.

Mechanisms and implications of COVID-19 transport into neural tissue

The neuropathogenicity of COVID-19 was reported shortly after detection of the virus when patients began reporting symptoms of diminished taste and smell, headaches, mental status changes, and more. As the virus spread, increasing data on viral symptoms in conjunction with novel theories on COVID-19 virulence factors indicated that the virus had neurotropic properties. Several mechanisms have been proposed detailing severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2) transport past the blood–brain barrier and into neural tissue. This chapter offers a comprehensive review of possible neurotropic mechanisms including transport via the angiotensin-converting enzyme 2 (ACE-2) receptor, transportation directly past or through the blood–brain barrier, transsynaptic neuronal transfer, and olfactory conduction. © 2023 Elsevier Inc. All rights reserved.

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

Gut Microbiome in COVID-19: New Insights

The last discovered organ of the human body is microbiome which is present at different sites in it. Gut microbiome consists of about 1000–1500 bacterial species and as regulated by genetic makeup, lifestyle, and environmental conditions, the gut microbiota of a healthy individual can comprise approximately 160 species of bacteria. Majority of gut microbiome consists of Firmicutes, Actinobacteria, Bacteroidetes, and to a lesser extent Proteobacteria, Euryarchaeota, Fusobacteria, and Verrucomicrobia. The gut-lung axis is involved in the migration of immune cells from gut to respiratory tract through circulation and encourages the host's ability to fight infections. The gut regulates the responses in lungs via host-acquired inflammatory mediators in the circulation. Dendritic cells located in the Peyer's patches of the intestine, macrophages, and Langerhans cells are the major antigen-presenting cells that play a vital role in the modulation and development of innate immune response. Gut microbiota interacts via the regulation and development of adaptive immune response. B and T lymphocytes are the key players of adaptive immunity. CD4 + T cells after activation differentiate into four major kinds of cell classes: (1) regulatory T cells (Treg), (2) Th2, (3) Th1, and (4) Th17 cells. Gut microbial interactions can induce the production of various types of immune cells as demonstrated by various studies. For instance, Clostridia induces the formation of Treg cells. Likewise, Bacteroides fragilis inhabiting the gut can incite the production of Th1 cells and production of T17 cells is stimulated by segmental filamentous bacteria. Gut microbiota also plays a vital role in the physiology and metabolism leading to the synthesis of various immunoregulatory metabolites such as SCFAs, antimicrobial peptides (AMPs), amino acids, and polyamines. SARS-CoV-2 virus entry to the cell is via ACE2 receptor present in respiratory epithelium and gut epithelium. This receptor is highly expressed (100 times more than in the lung) in the epithelial cells of the stomach, duodenum, ileum, and rectum as well as cholangiocytes and hepatocytes. High level of ACE2 receptor expressing in the gastrointestinal epithelial cells along with high-level co-expression of TMPRSS2 (cellular serine peptidase) causes coronavirus to infect gastrointestinal tract along with lungs leading to altered intestinal permeability and enterocyte malabsorption with symptoms of diarrhea in patients of COVID-19. Hence, COVID-19 patients with gastrointestinal symptoms have significantly longer duration of illness and viral clearance time than patients without any gastrointestinal symptoms. Obese patients with gut dysbiosis have decreased population of Bacteroides species. COVID-19 patients with type 2 diabetics have increased population of Fusobacterium, Ruminococcus, and Blautia with decreased population of Bacteroides, Bifidobacterium, Faecalibacterium, Akkermansia, and Roseburia. Diet with low fiber, high fat, and high carbohydrate causes gut dysbiosis. Intake of high-fiber diet consisting of whole grains, vegetables, and fruits induces growth of Bifidobacterium, Bacteroides, and Lactobacilli. Probiotics are nonpathogenic live organisms which are safe to be taken as dietary supplements. The major genera of probiotics are Lactobacillus, Bifidobacterium, and Saccharomyces. These probiotics increase the activity of T cells, NK cell, and polymorphonuclear cells. Prebiotics in the form of maize fiber, inulin, and polydextrose improves digestion and immunity. Hence, healthy gut microbiome with its strong immune intervention may bring recovery in COVID-19 patients. However, so far no published studies have reported that probiotics can be used as an adjunctive therapy in our fight against the SARS-CoV-2 infection. A far-reaching approach should consist of randomized, multicenter, controlled trials to explore the potential benefits of gut microbiome and how changes in dietary habits can be used as an add-on strategy against the COVID-19 pandemic. © The Author(s), under exc us ve licence to Springer Nature Singapore Pte Ltd. 2021.

Metformin in COVID-19: Is There a Role Beyond Glycemic Control?

Context: The coronavirus disease 2019 (COVID-19) pandemic is still a cause of worldwide health concern. Diabetes and its associated comorbidities are risk factors for mortality and morbidity in COVID-19. Selecting the right antidiabetic drug to achieve optimal glycemic control might mitigate some of the negative impacts of diabetes. Metformin continues to be the most widely administered antidiabetic agent. There is evidence of its beneficial outcome in COVID-19 independent of its glucose-lowering effect. Evidence Acquisition: A thorough literature search was conducted in PubMed, Google Scholar, Scopus, and Web of Science to identify studies investigating metformin in COVID-19. Result(s): Several overlapping mechanisms have been proposed to explain its antiviral properties. It could bring about conformational changes in the angiotensin-converting enzyme-2 receptor and decrease viral entry. The effects on the mammalian target of the rapamycin pathway and cellular pH have been proposed to reduce viral protein synthesis and replication. The immunomodulatory effects of metformin might counter the detrimental effects of hyperinflammation associated with COVID-19. Conclusion(s): These findings call for broader metformin usage to manage hyperglycemia in COVID-19.Copyright © 2023, International Journal of Endocrinology and Metabolism.

Epigenetic regulation of the COVID-19 pathogenesis: its impact on the host immune response and disease progression

Coronavirus disease 2019 (COVID-19) is highly infectious and may induce epigenetic alteration of the host immune system. Understanding the role of epigenetic mechanisms in COVID-19 infection is a clinical need to minimize critical illness and widespread transmission. The susceptibility to infection and progression of COVID-19 varies from person to person;pathophysiology substantially depends on epigenetic changes in the immune system and preexisting health conditions. Recent experimental and epidemiological studies have revealed the method of transmission and clinical presentation related to COVID-19 pathogenesis, however, the underlying pathology of variation in the severity of infection remains questionable. Epigenetic changes may also be responsible factors for multisystem association and deadly systemic complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients. Commonly, epigenetic changes are evoked by alteration of the host's immune response, stress, preexisting condition, oxidative stress response, external behavioral or environmental factors, and age. In addition, the viral infection itself might manipulate the host immune responses associated with inflammation by reprogramming epigenetic processes which are the susceptible factor for disease severity and death. As a result, epigenetic events such as histone modification and DNA methylation are implicated in regulating pro-inflammatory cytokines production by remodeling macrophage and T-cell activity towards inflammation, consequently, may also affect tissue repair and injury resolution process. This review aims to discuss the comprehensive understanding of the epigenetic landscape of COVID-19 disease progression that varies from person to person with supporting interdisciplinary prognosis protocol to overcome systemic impairment.

Effect of Mutations in the SARS-CoV-2 Spike RBD Region of Delta and Delta-Plus Variants on its Interaction with ACE2 Receptor Protein

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has undergone multiple significant mutations since its detection in 2019 in Wuhan, China. The emergence of new SARS-CoV-2 variants that can spread rapidly and undermine vaccine-induced immunity threatens the end of the COVID-19 pandemic. The delta variant (B.1.617.2) that emerged in India challenges efforts to control the COVID-19 pandemic. In addition to Delta, so-called Delta Plus sub-variants (B.1.617.2.1 and B.1.617.2.2) have become a new cause of global concern. Here we compare the interaction profile of RBD of the spike protein of the Delta and Delta-Plus variant of SARS-CoV-2 with the ACE2 receptor. From the molecular dynamics simulation, we observed the spike protein of Delta and Delta-Plus variant of SARS-CoV-2 utilizes unique strategies to have stable binding with ACE2. Using MM-GBSA/MM-PBSA algorithms, we found the binding affinity of spike protein of the Delta-variant-ACE2 complex is indeed high (GBTOT =-39.36 kcal mol-1, PBTOT=-17.52 kcal mol-1) in comparison with spike protein of Delta-Plus variant-ACE2 Complex (GBTOT =-36.83 kcal mol-1, PBTOT =-16.03 kcal mol-1). Stable binding of spike protein to ACE2 is essential for virus entry, and the interactions between them should be understood well for the treatment modalities. © 2022 by the authors.

Metabolites and metabolomics in COVID-19

Metabolomics is a comprehensive approach for identifying, quantifying, and characterizing entire metabolites in a biological system using a high-throughput technique. Metabolomics has great potential in discovering biochemical pathways and pathway interactions, disease diagnosis, and biomarker discovery. Viral infections induce changes in the host cell metabolism resulting in cellular reprogramming. In COVID-19, the dysregulation of host metabolites has been implemented in various aspects including diagnosis and management. This chapter summarizes various applications of metabolites and metabolomics approaches in COVID-19. © 2023 Elsevier Inc. All rights reserved.

Binding affinity improvement analysis of multiple-mutant Omicron on 2019-nCov to human ACE2 by in silico predictions.

CONTEXT: Since the outbreak of COVID-19 in 2019, the 2019-nCov coronavirus has appeared diverse mutational characteristics due to its own flexible conformation. One multiple-mutant strain (Omicron) with surprisingly infective activity outburst, and affected the biological activities of current drugs and vaccines, making the epidemic significantly difficult to prevent and control, and seriously threaten health around the world. Importunately exploration of mutant characteristics for novel coronavirus Omicron can supply strong theoretical guidance for learning binding mechanism of mutant viruses. What's more, full acknowledgement of key mutated-residues on Omicron strain can provide new methodology of the novel pathogenic mechanism to human ACE2 receptor, as well as the subsequent vaccine development. METHODS: In this research, 3D structures of 32 single-point mutations of 2019-nCov were firstly constructed, and 32-sites multiple-mutant Omicron were finally obtained based one the wild-type virus by homology modeling method. One total number of 33 2019-nCov/ACE2 complex systems were acquired by protein-protein docking, and optimized by using preliminary molecular dynamic simulations. Binding free energies between each 2019-nCov mutation system and human ACE2 receptor were calculated, and corresponding binding patterns especially the regions adjacent to mutation site were analyzed. The results indicated that one total number of 6 mutated sites on the Omicron strain played crucial role in improving binding capacities from 2019-nCov to ACE2 protein. Subsequently, we performed long-term molecular dynamic simulations and protein-protein binding energy analysis for the selected 6 mutations. 3 infected individuals, the mutants T478K, Q493R and G496S with lower binding energies -66.36, -67.98 and -67.09 kcal/mol also presents the high infectivity. These findings indicated that the 3 mutations T478K, Q493R and G496S play the crucial roles in enhancing binding affinity of Omicron to human ACE2 protein. All these results illuminate important theoretical guidance for future virus detection of the Omicron epidemic, drug research and vaccine development.

Sulfated polysaccharides act as baits to interfere with the binding of the spike protein (SARS-CoV-2) to the ACE2 receptor and can be administered through food.

Human civilization is experiencing a global crisis involving an unprecedented viral pandemic, with a high mortality rate, uncontrolled spread, and few effective drugs for treatment. Here, we critically evaluate how sulfated polysaccharides can be applied via foods to reduce the infectious process and increase the chances of an adequate immune response. The approach is directed to the infectious process by SARS-CoV-2 and protein S as a therapeutic focus. We discuss the antiviral activities of certain natural and specific sulfated polysaccharides that bind tightly to protein S. Finally, we identified that sulfated polysaccharides act as baits to interfere with the binding of the spike protein (SARS-CoV-2) to the ACE2 receptor and can be administered through food.

A Review on Catastrophic Evolution of SARS-CoV to SARS-CoV2: A Global Pandemic

The coronaviruses, belonging to the family Coronaviridae, have caused a massive pandemic in December 2019 after their previous outbreaks as SARS-CoV and MERS. The outbreak is believed to have originated from the seafood and live market in the Hubei province of China. The Rhinolophus species are the natural hosts of this virus. This virus caused pneumonia and took away many lives be-fore it was recognized as the novel Coronavirus. Very little information is available about the biology and nature of the novel Coronavirus. This article reviews multiple aspects encompassing its origin, epi-demiology, pathogenesis, symptoms, and the global statistics of spread. Acute respiratory distress syndrome (ARDS) is the key symptom of this condition. Angiotensin-converting enzyme 2 (ACE2) helps in the penetration of the virus into the target cells. Deeper research and understanding are essential for the identification of antibodies that inhibit ACE2 and can prevent viral replication. Drug design and control of disease are crucial. In countries like India, where plant diversity is extensive, it is prudent to focus on plant-based alternative drugs. Many attempts have been made to review and curate the drug discovery attempts using immuno-informatic and bioinformatic tools.Copyright © 2021 Bentham Science Publishers.

Coordinated Roadmap to Grip Pandemic COVID-19

Coronavirus disease 2019 named COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported in Wuhan city of Hubei Province of China become a global pandemic. Genomic sequencing of SARS-CoV-2 unveils which showed multiple mutations relative to SARS-CoV. SARS-CoV-2 showed a very high receptor-binding domain (RBD) affinity towards the ACE-2 receptor in host cells, similar to SARS. Lack of immediate supervision and diagnostic measures hurdles prevention and treatment strategies against COVID-19. However, from SARS and MERS epidemics, WHO launched SOLIDARITY, a strategic and technical advisory group for infection hazards (STAG-IH) for the regular supervision and alert, which identified the estimated risk of COVID-19 and recommended the health emergence program to respond COVID-19. This article will briefly review the rationale history, structural genome with mutation, pathogenesis, preventive measure, and targeted treatment strategy to handle this pandemic COVID-19.Copyright © 2021 Bentham Science Publishers.

The Outbreak of Novel Coronavirus-a New Type of Threat in 2020: Genesis, Detection, Treatment, and Management

Background: COVID-19 is a new, health-threatening infectious disease in the world in 2020 and is caused by a novel coronavirus SARS-CoV-2. As of July 13, 2020, 4,881,579 active cases of COVID-19 were diagnosed, and 571,080 deaths were reported globally. In India, 301,850 active cases and 23,187 deaths were reported. To date, no effective treatment is available against the deadly virus SARS-CoV-2. Drug manufacturers, institutional laboratories, and other organizations have started developing vaccines to combat COVID-19 infection. Method(s): Science Direct, Elsevier, PubMed, Scopus, and Nature databases were referred to know the current scenario of the disease. Moreover, recent data have been obtained from the World Health Orga-nization, Centre of Disease Control, case studies, newspapers, and Worldometer reports. Data of Vaccine Centre at the London School of Hygiene & Tropical Medicine, Clinicaltrials.gov, and US National Library of Medicine have also been accessed to obtain the latest information about ongoing clinical tri-als. Result(s): The primary source of the SARS-CoV-2 outbreak is connected to the Hunan seafood and live animal market in Wuhan city, Hubei Province, China. Like;SARS-CoV, and MERS-CoV, SARS-CoV-2 is also a zoonotic virus affecting the lower respiratory tract in humans. The pathogenesis of COVID-19 involves attachment of its Spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor in the lower respiratory tract in humans. The most common symptoms of COVID-19 are fever, cough, sore throat, fatigue, headache, myalgia, septic shock, and breathlessness. Few patients with COVID-19 infection experience diarrhea, vomiting, and abdominal pain. Currently, FDA approved drugs being used to treat COVID-19. Conclusion(s): This review article presents the importance of traditional Indian herbs recommended by AYUSH as precautionary and curative measures of COVID-19 until vaccines and drugs are made avail-able. Moreover, this article discussed the origin, symptoms, mode of transmission, management, and diagnostics techniques for the detection of the SARS-CoV-2 virus.Copyright © 2021 Bentham Science Publishers.

Lipid Lowering Natural Products Targeting hPCSK9 May Prevent the Severity of COVID-19 Infection

Background: The deadly outbreak of COVID-19 disease caused by novel SARS CoV2 has created an unprecedented global health crisis affecting every sectors of human life and enor-mous damage to world's economy. With >16.1 million infections and >650,000 deaths worldwide as of July 27, 2020, there is no treatment for this disease neither is there any available vaccine. Seri-ous research efforts are ongoing on all fronts including treatment, prevention and diagnosis to combat the spread of this infection. A number of targets that include both viral and host proteins have been identified and became part of intense investigation. In this respect the viral surface spike (S) glycoprotein caught the attention most. It is cleaved by multiple host proteases to allow recognition by host receptor human Angiotensin Converting Enzyme2 (hACE2) leading to fusion and viral re-plication. Natural products, small compounds, antioxidants, peptides, proteins, oligonucleotides, antibodies and other compounds are under investigation for development of antiviral agents against COVID-19. Objective(s): Recently cholesterol lowering phytocompounds Quercetin, Swertiamarin and Berberine which promote human Low Density Lipoprotein Receptor (hLDLR) via inhibition of human Pro-protein Convertase Subtilisin Kexin9 (hPCSK9) have been shown to block viral infections caused by ebola, influenza, Respiratory Syncytial Virus (RSV), Hepatitis C virus (HCV) and other RNA type viruses. Since SARS CoV2 is a RNA virus with similar genetic structure and infection machin-ery, it is hypothesised that these phytocompounds may also exhibit antiviral property against COVID-19. Method(s): Our above concept is based on recently published studies as well as our herein presented in silico modeling and computational data which suggested strong interactions of hPCSK9 with above phytocompounds and most importantly with hACE2 following its complexation with receptor binding domain (RBD) of SARS CoV2 S protein. Result(s): These results and a proposed schematic model showing association of hPCSK9 with SARS CoV2 infection are presented in this manuscript. It is proposed that hPCSK9 plays the role of a co-receptor in binding with hACE2:RBD complex and thereby facilitates viral fusion. Conclusion(s): Our studies suggest that PCSK9 inhibitors may provide beneficial effect against COVID-19 infection by retarding viral fusion through displacement of bound hPCSK9 from its complex with ACE2:RBD of SARS CoV2 S protein.Copyright © 2021 Bentham Science Publishers.

SARS-CoV-2 Therapy: Old Drugs as New Interventions

An outburst of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a grave threat to global health and the economy. As of May 13, 2020, a total of 42,81,838 cases have been confirmed, with over 2,92,376 deaths worldwide. In India, 75,048 cases have been reported to date with 2,440 deaths. Management of this new coronavirus (COVID19) has mainly focused on infection prevention, case detection, monitoring, and supportive care. As there is no vaccine or specific antiviral treatment for human SARS-CoV-2, therefore identifying the drug treatment options as soon as possible is critical for the response to the COVID19 outbreak. Pro-inflammatory cascade and cytokine storm play a key role in the pathogenesis of new coronavirus. A large number of therapeutic interventions such as antiviral, antimalarial, convalescent plasma therapy, BCG vaccine, mTOR inhibi-tors, Tissue Plasminogen Activator, Human monoclonal antibodies, Anti-parasitic agents, Immunoen-hancers, Nutritional interventions, JAK-STAT signaling inhibitors, ACE2 receptor modulators, and An-giotensin II receptor blockers have been either tried or suggested for effective treatment of patients with SARS-CoV-2 disease. Hence, we recommend that all the above potential interventions must be imple-mented in terms of their safety and efficacy through proper clinical experiments to control the emerging SARS-CoV-2 disease.Copyright © 2021 Bentham Science Publishers.

Chemi-Informatic Approach to Investigate Putative Pharmacoactive Agents of Plant Origin to Eradicate COVID-19

Background: The scientific community has supported the medicinal flora of ancient as well as modern times in extracting chemicals, which holds therapeutic potential. In many previous studies, Amentoflavone discovered as an anti-viral agent, and it is present as a bioactive constituent in many plants of different families like Selaginellaceae, Euphorbiaceae, and Calophyllaceae. Withania somnifera (Ashwagandha) is already considered a significant anti-viral agent in traditional medicine, and it is the main source of Somniferine-A and Withanolide-B. Objective(s): In this study, phytochemicals such as withanolide-b, somniferine-a, stigmasterol, amentoflavone, and chavicine were analyzed to screen protein inhibitors, out of them;such proteins are involved in the internalization and interaction of SARS-CoV-2 with human cytological domains. This will help in developing a checkpoint for SARS-CoV-2 internalization. Method(s): Chemi-informatic tools like basic local alignment search tool (BLAST), AutoDock-vina, SwissADME, MDWeb, Molsoft, ProTox-II, and LigPlot were used to examine the action of pharmacoactive agents against SARS-CoV-2. The tools used in the study were based on the finest algorithms like artificial neural networking, machine learning, and artificial intelligence. Result(s): On the basis of binding energies less than equal to-8.5 kcal/mol, amentoflavone, stigmasterol, and somniferine-A were found to be the most effective against COVID-19 disease as these chemical agents exhibit hydrogen bond interactions and competitively inhibit major proteins (SARS-CoV-2 Spike, Human ACE-2 receptor, Human Furin protease, SARS-CoV-2 RNA binding protein) that are involved in its infection and pathogenesis. Simulation analysis provides more validity to the selection of the drug candidate Amentoflavone. ADMET properties were found to be in the feasible range for putative drug candidates. Conclusion(s): Computational analysis was successfully used for searching pharmacoactive phytochemicals like Amentoflavone, Somniferine-A, and Stigmasterol that can bring control over COVID-19 expansion. This new methodology was found to be efficient, as it reduces monetary expenditures and time consumption. Molecular wet-lab validations will provide approval for finalizing our selected drug model for controlling the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Acute Mesenteric Thrombosis, Small Intestine Necrosis and Peritonitis as a Complication of Covid-19 - a Case Report

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to a family of ribonucleic acid (RNA) viruses, causing novel coronavirus disease 2019 (COVID-19). Because of a global inflammatory response and endothelial damage, COVID-19 may predispose to coagulation disorders and severe thrombotic events. Case presentation. A 62-year-old man patient was admitted for COVID-19 pneumonia and abdominal pain for 10 days. Because of the rapid deterioration of the clinical status, shock and evidence of peritoneal irritation, the patient was consulted by a surgeon. The native spiral computed tomography (CT) of the abdomen detected enlarged colon filled with air collections and hydro-aeric levels. The surgical intervention revealed diffuse peritonitis with necrosis of the distal ileum secondary to mesenteric thrombosis. A partial resection of the ileum was done. The histological examination showed an infarcted small bowel, with hemorrhage, vascular thrombosis, and signs of necrotizing endovasculitis. Conclusions. SARS-CoV-2 binds to ACE2 receptor, which results in increased signalling by thrombin receptors on platelet and endothelial cells, leading to coagulopathy. In older patients presenting with abdominal pain, shock and peritonitis, the most common underlying cause is mesenteric thrombosis which could be a complication of COVID-19.Copyright © 2022 Balkan Medical Union.

Mechanism of Cardiac Pathogenesis and Cardiotoxicity of Anti-COVID-19 Drugs

Novel coronavirus (nCoV-19) infection has been declared a pandemic by WHO. More than 223 countries are under the attack of this emergency situation. Primarily, pneumocytes encountered by the nCoV-19 via ACE-2 receptor cause pulmonary edema, damage to alveolar cells, production of inflammatory cells, and hypoxia. It has been found that patients with co-existing cardiovascular diseases are more prone to the infection, and severe cardiovascular dysfunction was further observed when infected with nCoV-19. There is no substantial mechanism available for the pathogenesis of this cardiovascular dysfunction;therefore, we herein present a possible mechanistic approach of cardiotoxicity by nCov-19 infection. The hypothesis of this study is based on immunopathology of nCoV-19 in pneumocytes, presence of ACE-2 on cardiomyocytes membrane, cytokine storm, genomic analysis of virus in cardiac tissue, and several reports published on the cardiovascular complications in nCoV-19 across the globe. We have also analyzed the cardiotoxic profile of recently used repurposed and investigational drugs and highlighted their possible cardiotoxic consequences and drug interactions with cardiovascular medicines, such as statins and anti-coagulants.Copyright © 2021 Bentham Science Publishers.

Ferrets: A powerful model of SARS-CoV-2.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social, economic, and health burdens worldwide. Despite considerable efforts to combat coronavirus disease 2019 (COVID-19), various SARS-CoV-2 variants have emerged, and their underlying mechanisms of pathogenicity remain largely unknown. Furthermore, effective therapeutic drugs are still under development. Thus, an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections. Currently, several animal models, including mice, hamsters, ferrets, and non-human primates (NHPs), have been established to study COVID-19. Among them, ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study. Here, we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis, therapeutic agents, and vaccines, and provide a perspective on the role of these models in preventing COVID-19 spread.

Coronaviruses Use ACE2 Monomers as Entry-Receptors.

The angiotensin-converting enzyme 2 (ACE2) has been identified as entry receptor on cells enabling binding and infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via trimeric spike (S) proteins protruding from the viral surface. It has been suggested that trimeric S proteins preferably bind to plasma membrane areas with high concentrations of possibly multimeric ACE2 receptors to achieve a higher binding and infection efficiency. Here we used direct stochastic optical reconstruction microscopy (dSTORM) in combination with different labeling approaches to visualize the distribution and quantify the expression of ACE2 on different cells. Our results reveal that endogenous ACE2 receptors are present as monomers in the plasma membrane with densities of only 1-2 receptors µm-2 . In addition, binding of trimeric S proteins does not induce the formation of ACE2 oligomers in the plasma membrane. Supported by infection studies using vesicular stomatitis virus (VSV) particles bearing S proteins our data demonstrate that a single S protein interaction per virus particle with a monomeric ACE2 receptor is sufficient for infection, which provides SARS-CoV-2 a high infectivity.