The Ineluctable Role of ACE-2 Receptors in SARS COV-2 Infection and Drug Repurposing as a Plausible SARS COV-2 Therapy : A Concise Treatise

2021 ◽  
Vol 21 ◽  
Author(s):  
Sherin Joseph ◽  
Bhagyalakshmi Nair ◽  
Lekshmi R. Nath
Keyword(s):  
Inflammatory Responses ◽  
Transmission Rate ◽  
Drug Repurposing ◽  
Severe Pneumonia ◽  
Organ Damage ◽  
Peptidase Activity ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Organ Systems ◽  
Lung Histology

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the COVID-19 infectious disease that spreads via the respiratory route and has reached a drastic level of a global pandemic. Symptoms of COVID-19 may vary from mild (fever, dry cough, shortness of breath) to severe pneumonia-like respiratory symptoms as exacerbation of disease occurs. Unlike SARS-CoV, the SARS-CoV-2 has a higher binding affinity to ACE-2 receptors which signify its higher transmission rate from person to person. Even though ACE-2 is significant in the renin-angiotensin-aldosterone system (RAAS) regulation that exhibits protection to various organs, they play a significant role in COVID-19 disease pathogenesis. Viral interferences with the ACE-2 peptidase activity are found in SARS-CoV-2 infected patients leading to pro-inflammatory responses, hypertension and multi-organ damage. Angiotensin-converting enzyme-2 is constrained to a variety of organ systems but surface ACE-2 receptors on lung epithelia are largely affected, that lead to pathological alterations in lung histology which may progress to respiratory failure. The viral tropism mainly occurs by the attachment to the angiotensin-converting enzymes-2 receptors in the host cell, thus drugs targeting ACE-2 expressions may arise as the future therapeutic strategy to combat COVID-19 infections.The innovative approach of repurposing of drugs has shown temporary effectiveness to the rising pandemic. This article mainly focuses on the prominence of ACE-2 receptors which are expressed during the COVID infections and repurposing strategy of available drug therapies.

scholarly journals Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19

2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  
Keyword(s):  
Organ Damage ◽  
Multiple Organ ◽  
Global Pandemic ◽  
Organ Systems ◽  
Future Challenges ◽  
The Central Nervous System ◽  
The Impact ◽  
Collaborative Efforts ◽  
The Brain

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

scholarly journals SARS-CoV-2, ACE2 expression, and systemic organ invasion

2020 ◽  
Author(s):  
Usman M Ashraf ◽  
Ahmed A Abokor ◽  
Jonnelle M. Edwards ◽  
Emily W. Waigi ◽  
Rachel S. Royfman ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Normal Function ◽  
Multiple Organ ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
Global Pandemic ◽  
Organ Systems ◽  
Novel Coronavirus ◽  
Severe Respiratory Illness ◽  
Organ Invasion

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

scholarly journals Metabolic Syndrome “Interacts” With COVID-19

2020 ◽  
Author(s):  
Zeling Guo ◽  
Shanping Jiang ◽  
Zilun Li ◽  
Sifan Chen
Keyword(s):  
Metabolic Disorders ◽  
Distress Syndrome ◽  
Metabolic Diseases ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Symptomatic Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Treatment And Prevention ◽  
Global Pandemic ◽  
Metabolic Comorbidities

COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a global pandemic and poses a great threat to public health and society in general. SARS-CoV-2 invades cells via its spike protein, which initiates endocytosis via its binding to host receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion after being cleaved by the serine protease, TMPRSS2. The most common clinical manifestations are fever, dry cough, fatigue and abnormalities on chest computed tomography (CT). However, some patients rapidly progress to severe pneumonia and develop acute respiratory distress syndrome (ARDS). Furthermore, SARS-CoV-2 triggers a severe cytokine storm, which may explain the deterioration of pre-existing metabolic disorders. Interestingly, conversely, underlying metabolic-related diseases, including hypertension, diabetes, cardiovascular disease, etc., are associated with progression and poor prognosis of COVID-19. The putative mechanisms are dysregulation of ACE2, impaired immunity especially uncontrolled hyperinflammation, hypercoagulability, etc. In this review, we summarize the crosstalk between COVID-19 and metabolic diseases and propose that in addition to controlling COVID-19, more intensive attention should be paid to the symptomatic treatment and prevention of pre-existing and foreseeable metabolic comorbidities.

COVID-19 Global Pandemic Fight by Drugs: A Mini-Review on Hope and Hype

2021 ◽  
Vol 18 ◽  
Author(s):  
Sunil Tekale ◽  
Vishnu Gore ◽  
Pravin Kendrekar ◽  
Shivaji Thore ◽  
László Kótai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Transmission Rate ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Current Medical ◽  
Medical Emergency ◽  
Global Pandemic ◽  
Global Issue ◽  
The City

: Coronavirus disease 2019 (Covid-19) is caused by the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) was firstly identified in the city of Wuhan of China in December 2019, which was spread and become a global issue due to its high transmission rate. To date, the outbreak of COVID-19 has resulted in infection to 150,356,672 people and the death of 3,167,010 patients. It paralyzed the economy of all the countries worldwide. Unfortunately, no specific FDA-approved antiviral treatment or vaccine is available to curb the outbreak. Considering the possible mutations of SARS-CoV-2, the current medical emergency required a longer time for drug design and vaccine development. Drug repurposing is a promising option for potent therapeutic against the pandemic. The present review encompasses various drugs or appropriate combinations of already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeutic candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the disease.

COVID-19: Update on Pathogenesis and Treatment Strategies

2020 ◽  
Vol 16 (1) ◽  
pp. 1-5
Author(s):  
Rakesh K. Chauhan ◽  
Pramod K. Sharma ◽  
Shikha Srivastava
Keyword(s):  
Monoclonal Antibody ◽  
Plasma Membrane ◽  
Human Monoclonal Antibody ◽  
Cardiac Injury ◽  
Treatment Strategies ◽  
Severe Pneumonia ◽  
Ground Glass Opacity ◽  
Golgi Membrane ◽  
Virus Particles ◽  
Global Pandemic

COVID-19 (Coronavirus disease) is the most contagious virus, which has been characterized as a global pandemic by WHO. The pathological cycle of COVID-19 virus can be specified as RNAaemia, severe pneumonia, along with the Ground-glass opacity (GGO), and acute cardiac injury. The S protein of Coronavirus has been reported to be involved in the entry of the virus into the host cell, which can be accomplished by direct membrane fusion between the virus and plasma membrane. In the endoplasmic reticulum or Golgi membrane, the newly formed enveloped glycoproteins are introduced. The spread of disease occurs due to contact and droplets unleashed by the vesicles holding the virus particles combined with the plasma membrane to the virus released by the host. The present manuscript describes the pathogenesis of COVID-19 and various treatment strategies that include drugs such as chloroquine and hydroxychloroquine, an anti-malarial drug, antibodies: SARS-CoV-specific human monoclonal antibody CR3022 and plasma treatment facilitate the therapeutic effect.

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

scholarly journals Literature Review of the Implications of Exercise Rehabilitation Strategies for SARS Patients on the Recovery of COVID-19 Patients

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 590
Author(s):  
Wei Cui ◽  
Ting Ouyang ◽  
Ye Qiu ◽  
Di Cui
Keyword(s):  
Exercise Intervention ◽  
Treatment Strategies ◽  
Severe Pneumonia ◽  
Clinical Indicators ◽  
Exercise Rehabilitation ◽  
Global Pandemic ◽  
Epidemic Period ◽  
Local Risk ◽  
And Control ◽  
Rehabilitation Strategies

As a global pandemic, COVID-19 shows no sign of letting up. With the control of the epidemic in China, the proportion of patients with severe and critical diseases being cured and discharged from hospital has increased, and the recovery of COVID-19 patients has become an important issue that urgently needs attention and solutions. By summarizing the exercise rehabilitation strategies and progress of SARS in 2003, this paper analyzed the differences in clinical indicators and recovery characteristics of severe pneumonia caused by the two viruses, and provided comprehensive exercise guidance and intervention strategies for COVID-19 patients for rehabilitation and nursing by referring to the problems and treatment strategies in the rehabilitation and nursing work of SARS. In the post-epidemic period, China will build a multi-dimensional epidemic prevention system by improving the effectiveness of mass training and strengthening local risk prevention and control. This paper discusses the exercise rehabilitation strategy of SARS patients after recovery, which has guiding significance for exercise intervention and scientific fitness of COVID-19 patients after recovery during epidemic prevention period.

scholarly journals Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3213
Author(s):  
Alon Ben David ◽  
Eran Diamant ◽  
Eyal Dor ◽  
Ada Barnea ◽  
Niva Natan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
High Throughput Screening ◽  
Cell Attachment ◽  
Drug Repurposing ◽  
Heparin Sodium ◽  
Compound Libraries ◽  
Global Pandemic ◽  
Ic50 Values ◽  
Binding Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC®1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 µg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.

scholarly journals Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

2021 ◽  
Vol 9 (6) ◽  
pp. 1211
Author(s):  
Mahnaz Norouzi ◽  
Shaghayegh Norouzi ◽  
Alistaire Ruggiero ◽  
Mohammad S. Khan ◽  
Stephen Myers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Factor ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Immune System Dysfunction ◽  
Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

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