Peculiar Histopathological Alterations of Enterocytes in A Coronavirus Disease 2019 Patient with Mycobacterial Tuberculosis Co-Infection

Abstract Background: The ongoing novel Coronavirus Disease 2019 (COVID-19) pandemic is principally defined by its respiratory symptoms. While it is clear that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can affect the gastrointestinal tract (GIT) and the pathogenesis of coronavirus disease 2019 is better understood, the exact pathological alterations following infection require further investigation. The purpose of this paper is to report and share our histopathological findings from a right hemicolectomy specimen of a confirmed COVID-19 positive case, which exhibited a Mycobacterium Tuberculosis co-infection.Methods:Microscopic sections from right hemicolectomy specimen were appropriately stained and studied by two anatomical pathologists. Additionally, we searched PubMed and Google Scholar databases for reports/observations regarding pathological alterations of the intestine following COVID-19 infection.Results:Histological sections showed novel peculiar pathological alterations in the terminal ileal mucosa involving principally absorptive enterocytes with evidence of striking cellular injury as well as prominent erythrophagocytosis in the mesenteric lymph nodes. No specific pathological alterations were observed in the appendix or colon. The characteristic pathological features of Mycobacterium Tuberculosis infection were also observed throughout the specimen.Conclusions:Our observations showed that the novel SARS-CoV-2 can affect the gastrointestinal tract, causing epithelial injury and pathological alterations attributed to its ability to infect absorptive enterocytes by interacting with the Angiotensin Converting Enzyme-2 (ACE2) receptor. These pathological findings could be regarded as viral cytopathic changes and should be considered when evaluating gastrointestinal specimens from COVID-19 infected patients.

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Peculiar Histopathological Alterations of Enterocytes in a Patient Co-infected with Severe Acute Respiratory Syndrome Coronavirus 2 and Mycobacterium Tuberculosis: A Case Study

10.21203/rs.3.rs-362390/v2 ◽

2021 ◽

Author(s):

Rana AL-Zaidi ◽

Nasir AL-Noor ◽

Adel Habbash

Keyword(s):

Mycobacterium Tuberculosis ◽

Severe Acute Respiratory Syndrome ◽

Right Hemicolectomy ◽

The Novel ◽

Pathological Findings ◽

Epithelial Injury ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus ◽

Absorptive Enterocytes

Abstract The ongoing novel coronavirus disease 2019 (COVID-19) is principally defined by its respiratory symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the gastrointestinal tract (GIT) and although the pathogenesis of COVID-19 is understood, the exact pathological alterations following infection require further investigation. Here, we report our histopathological findings from a right hemicolectomy specimen from a patient coinfected with COVID-19 and Mycobacterium tuberculosis. Our observations showed that the novel SARS-CoV-2 can affect the GIT, causing epithelial injury and pathological alterations attributed to its ability to infect absorptive enterocytes by interacting with the angiotensin converting enzyme-2 (ACE2) receptor. These pathological findings are regarded as viral cytopathic changes and should be considered when evaluating gastrointestinal specimens from COVID-19-infected patients.

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COVID-19 Vaccination: From Interesting Agent to the Patient

Vaccines ◽

10.3390/vaccines9020120 ◽

2021 ◽

Vol 9 (2) ◽

pp. 120

Author(s):

Anis Daou

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Gastrointestinal Tract ◽

Circulatory System ◽

The Novel ◽

Lead Compound ◽

Fda Approval ◽

The World ◽

The Central Nervous System ◽

Novel Coronavirus

The vaccination for the novel Coronavirus (COVID-19) is undergoing its final stages of analysis and testing. It is an impressive feat under the circumstances that we are on the verge of a potential breakthrough vaccination. This will help reduce the stress for millions of people around the globe, helping to restore worldwide normalcy. In this review, the analysis looks into how the new branch of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) came into the forefront of the world like a pandemic. This review will break down the details of what COVID-19 is, the viral family it belongs to and its background of how this family of viruses alters bodily functions by attacking vital human respiratory organs, the circulatory system, the central nervous system and the gastrointestinal tract. This review also looks at the process a new drug analogue undergoes, from (i) being a promising lead compound to (ii) being released into the market, from the drug development and discovery stage right through to FDA approval and aftermarket research. This review also addresses viable reasoning as to why the SARS-CoV-2 vaccine may have taken much less time than normal in order for it to be released for use.

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Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽

10.3390/molecules26010057 ◽

2020 ◽

Vol 26 (1) ◽

pp. 57

Author(s):

Zhi-Ling Zhu ◽

Xiao-Dan Qiu ◽

Shuo Wu ◽

Yi-Tong Liu ◽

Ting Zhao ◽

...

Keyword(s):

Therapeutic Strategy ◽

Blocking Effect ◽

Spike Protein ◽

Binding Affinities ◽

The Novel ◽

Converting Enzyme ◽

Primary Method ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus ◽

Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

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ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

Human Genomics ◽

10.1186/s40246-021-00304-9 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Sally Badawi ◽

Bassam R. Ali

Keyword(s):

Cell Surface ◽

Angiotensin Converting Enzyme ◽

The Novel ◽

Converting Enzyme ◽

Post Translational Modifications ◽

Angiotensin Converting Enzyme 2 ◽

Viral Attachment ◽

Novel Coronavirus ◽

Effective Medication ◽

Potential Use

AbstractWith the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

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Inhibition of Escherichia coli Translocation from the Gastrointestinal Tract by Normal Cecal Flora in Gnotobiotic or Antibiotic-Decontaminated Mice

Infection and Immunity ◽

10.1128/iai.29.3.1073-1081.1980 ◽

1980 ◽

Vol 29 (3) ◽

pp. 1073-1081

Author(s):

Rodney D. Berg

Keyword(s):

Escherichia Coli ◽

Gastrointestinal Tract ◽

Lymph Nodes ◽

Bacterial Flora ◽

Specific Pathogen Free ◽

Mesenteric Lymph Nodes ◽

E Coli ◽

Mesenteric Lymph ◽

Specific Pathogen ◽

Gnotobiotic Mice

Escherichia coli C25 maintained population levels of 10 9 to 10 10 per g of cecum and translocated to 100% of the middle mesenteric lymph nodes in gnotobiotic mice monoassociated with E. coli C25. Intragastric inoculation of these mice with the cecal contents from specific-pathogen-free mice reduced the population levels of E. coli C25 to 10 6 per g of cecum and completely inhibited translocation to the mesenteric lymph nodes. Intragastric inoculation with heat-treated, Formalintreated, or filtered cecal contents did not reduce the population levels of E. coli C25 or reduce the incidence of translocation of E. coli C25 to the mesenteric lymph nodes. Thus, viable bacteria apparently are required in the cecal contents inocula to reduce the population levels and the incidence of translocation of E. coli C25. Treatment with streptomycin plus bacitracin decreased the anaerobic bacterial levels in these gnotobiotic mice, allowing increased population levels of E. coli C25 and increased translocation to the mesenteric lymph nodes. E. coli C25 also translocated to the mesenteric lymph nodes of specific-pathogen-free mice treated with streptomycin and bacitracin before colonization with E. coli C25. The high cecal population levels of E. coli C25 in these antibiotic-decontaminated specific-pathogen-free mice apparently overwhelm any barrier to translocation exerted by the immunologically developed lamina propria of the specific-pathogen-free mice. Inoculation of gnotobiotic mice with a cecal flora also reduced the population levels of an indigenous strain of E. coli with a concomitant inhibition of translocation of the indigenous E. coli to the mesenteric lymph nodes. Thus, bacterial antagonism of the gastrointestinal population levels of certain indigenous bacteria, such as E. coli , by other members of the normal bacterial flora appears to be an important defense mechanism confining bacteria to the gastrointestinal tract.

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Quinoline and Quinazoline Alkaloids against COVID-19: An In Silico Multitarget Approach

Journal of Chemistry ◽

10.1155/2021/3613268 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Esraa M. O. A. Ismail ◽

Shaza W. Shantier ◽

Mona S. Mohammed ◽

Hassan H. Musa ◽

Wadah Osman ◽

...

Keyword(s):

Antimalarial Activity ◽

The Novel ◽

Socioeconomic Impacts ◽

Health Crisis ◽

Natural Sources ◽

Angiotensin Converting Enzyme 2 ◽

Main Protease ◽

Recent Outbreak ◽

Novel Coronavirus ◽

Potential Inhibitors

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts. Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources. In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19. Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles. The results identified a number of potential inhibitors. Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2. These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19.

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Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

10.21203/rs.3.rs-29037/v2 ◽

2020 ◽

Author(s):

Xingyi Guo ◽

Zhishan Chen ◽

Yumin Xia ◽

Weiqiang Lin ◽

Hongzhi Li

Keyword(s):

Genetic Variation ◽

The Novel ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Missense Variants ◽

Catalytic Metal ◽

Using Data ◽

Novel Coronavirus ◽

Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

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Arterial Hypertension as a Risk Comorbidity Associated with COVID-19 Pathology

International Journal of Hypertension ◽

10.1155/2020/8019360 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Alexander Kamyshnyi ◽

Inna Krynytska ◽

Victoriya Matskevych ◽

Mariya Marushchak ◽

Oleh Lushchak

Keyword(s):

Arterial Hypertension ◽

Pressure Control ◽

The Novel ◽

Global Public Health ◽

Angiotensin Converting Enzyme 2 ◽

Cardiovascular Comorbidities ◽

Public Health Challenge ◽

Novel Coronavirus ◽

Ace2 Gene

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an ongoing global public health challenge. Current clinical data suggest that, in COVID-19 patients, arterial hypertension (AH) is one of the most common cardiovascular comorbidities; it can worsen outcomes and increase the risk of admission to intensive care unit (ICU). The exact mechanisms through which AH contributes to the poor prognosis in COVID-19 are not yet clear. The putative relationship between AH and COVID-19 may be linked to the role of angiotensin-converting enzyme 2 (ACE2), a key element of the AH pathophysiology. Another mechanism connecting AH and COVID-19 is the dysregulation of the immune system resulting in a cytokine storm, mediated by an imbalanced response of T helper cells subtypes. Therefore, it is essential to optimize blood pressure control in hypertensive patients and monitor them carefully for cardiovascular and other complications for the duration of COVID-19 infection. The question whether AH-linked ACE2 gene polymorphisms increase the risk and/or worsen the course of SARS-CoV-2 infection should also receive further consideration.

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Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Nature Communications ◽

10.1038/s41467-020-18319-6 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Jinsung Yang ◽

Simon J. L. Petitjean ◽

Melanie Koehler ◽

Qingrong Zhang ◽

Andra C. Dumitru ◽

...

Keyword(s):

Binding Pocket ◽

Living Cells ◽

Host Cells ◽

The Novel ◽

Angiotensin Converting Enzyme 2 ◽

Force Microscopy ◽

Binding Interface ◽

Atomic Force ◽

Viral Glycoproteins ◽

Novel Coronavirus

Abstract Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

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Fluid and Electrolyte Disturbances in COVID-19 and Their Complications

BioMed Research International ◽

10.1155/2021/6667047 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Mohammad Pourfridoni ◽

Seyede Mahsa Abbasnia ◽

Fateme Shafaei ◽

Javad Razaviyan ◽

Reza Heidari-Soureshjani

Keyword(s):

Kidney Injury ◽

Respiratory Illness ◽

The Novel ◽

Acute Respiratory Illness ◽

Gi Tract ◽

Angiotensin Converting Enzyme 2 ◽

Intensive Care Patients ◽

Electrolyte Disturbances ◽

Novel Coronavirus ◽

Tract Damage

The novel coronavirus disease 2019 (COVID-19) is the cause of an acute respiratory illness which has spread around the world. The virus infects the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptors. Due to the presence of ACE2 receptors in the kidneys and gastrointestinal (GI) tract, kidneys and GI tract damage arising from the virus can be seen in patients and can cause acute conditions such as acute kidney injury (AKI) and digestive problems for the patient. One of the complications of kidneys and GI involvement in COVID-19 is fluid and electrolyte disturbances. The most common ones of these disorders are hyponatremia, hypernatremia, hypokalemia, hypocalcemia, hypochloremia, hypervolemia, and hypovolemia, which if left untreated, cause many problems for patients and even increase mortality. Fluid and electrolyte disturbances are more common in hospitalized and intensive care patients. Children are also at greater risk for fluid and electrolyte disturbances complications. Therefore, clinicians should pay special attention to the fluid and electrolyte status of patients. Changes in fluid and electrolyte levels can be a good indicator of disease progression.

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