An Update of Coronavirus Disease 2019 (COVID-19): An Essential Brief for Clinicians

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

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Pediatric COVID-19 and the Factors That May Mitigate Its Clinical Course

Journal of Child Science ◽

10.1055/s-0040-1717077 ◽

2020 ◽

Vol 10 (01) ◽

pp. e137-e140

Author(s):

Mosaad Abdel-Aziz ◽

Nada M. Abdel-Aziz ◽

Dina M. Abdel-Aziz ◽

Noha Azab

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

Clinical Course ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Angiotensin Converting Enzyme 2 ◽

Compulsory Vaccination ◽

Specific Factors ◽

Novel Coronavirus ◽

Radiographic Data

AbstractThe clinical manifestations of novel coronavirus disease 2019 (COVID-19) vary from mild flu-like symptoms to severe fatal pneumonia. However, children with COVID-19 may be asymptomatic or may have mild clinical symptoms. The aim of this study was to investigate clinical features of pediatric COVID-19 and to search for the factors that may mitigate the disease course. We reviewed the literature to realize the clinical features, laboratory, and radiographic data that may be diagnostic for COVID-19 among children. Also, we studied the factors that may affect the clinical course of the disease. Fever, dry cough, and fatigue are the main symptoms of pediatric COVID-19, sometimes flu-like symptoms and/or gastrointestinal symptoms may be present. Although some infected children may be asymptomatic, a recent unusual hyperinflammatory reaction with overlapping features of Kawasaki's disease and toxic shock syndrome in pediatric COVID-19 has been occasionally reported. Severe acute respiratory syndrome-coronvirus-2 (SARS-CoV-2) nucleic acid testing is the corner-stone method for the diagnosis of COVID-19. Lymphocyte count and other inflammatory markers are not essentially diagnostic; however, chest computed tomography is highly specific. Factors that may mitigate the severity of pediatric COVID-19 are home confinement with limited children activity, trained immunity caused by compulsory vaccination, the response of the angiotensin-converting enzyme 2 receptors in children is not the same as in adults, and that children are less likely to have comorbidities. As infected children may be asymptomatic or may have only mild respiratory and/or gastrointestinal symptoms that might be missed, all children for families who have a member diagnosed with COVID-19 should be investigated.

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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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ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

10.26434/chemrxiv.12335933.v1 ◽

2020 ◽

Author(s):

Saroj Kumar Panda ◽

Parth Sarthi Sen Gupta ◽

Satyaranjan Biswal ◽

Abhik Kumar Ray ◽

Malay Kumar Rana

Keyword(s):

Principal Component ◽

Host Cells ◽

Spike Protein ◽

Peptide Inhibitor ◽

The Novel ◽

Receptor Binding Domain ◽

Converting Enzyme ◽

Inhibition Assay ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus

<p>SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress. </p>

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Acute Pulmonary Embolism in Coronavirus Disease 2019

10.21203/rs.3.rs-41996/v1 ◽

2020 ◽

Author(s):

Yanan Guo ◽

Wenwu Sun ◽

Yanli Liu ◽

Yanling Lv ◽

Su Zhao ◽

...

Keyword(s):

Pulmonary Embolism ◽

Clinical Manifestations ◽

Signs And Symptoms ◽

Pulmonary Angiography ◽

Severe Condition ◽

Computed Tomographic ◽

Number Of Patients ◽

Wells Score ◽

Computed Tomographic Pulmonary Angiography ◽

D Dimer

Abstract Background Pulmonary embolism is a severe condition prone to misdiagnosis given its nonspecific signs and symptoms. Previous studies on the pneumonia outbreak caused by coronavirus disease 2019 (COVID-19) showed a number of patients with elevated d-dimer, whether those patients combined with pulmonary embolism got our attention. Methods Data on clinical manifestations, laboratory and radiological findings, treatment, and disease progression of 19 patients with laboratory-confirmed COVID-19 pneumonia,who completed computed tomographic pulmonary angiography (CTPA) during hospitalization in the Central Hospital of Wuhan from January 2 to March 26, 2020, were reviewed. Results Of the 19 suspected pulmonary embolism and subjected to CTPA patients, six were diagnosed with pulmonary embolism. The Wells’ score of the six patients with pulmonary embolism was 0–1, which suggested a low risk of pulmonary embolism. The median level of d-dimers collected at the day before or on the day of CTPA completion in the patients with pulmonary embolism was 18.36 (interquartile range [IQR]: 6.69–61.46) µg/mL, which was much higher than that in the patients without pulmonary embolism (median 9.47 [IQR: 4.22–28.02] µg/mL). Of the 6 patients diagnosed with pulmonary embolism, all patients received anticoagulant therapy, 5 of which survived and were discharged and 1 died. Conclusion A potential causal relationship exists between COVID-19 infection and pulmonary embolism, but whether this phenomenon is common remains uncertain. The clinical manifestations of COVID-19 patients who developed pulmonary embolism are similar to those of patients with increased d-dimer alone, prompting a significant challenge on differential diagnoses.

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Covid-19: An Insight over the Third Respiratory Global Emergency of the Century

Coronaviruses ◽

10.2174/2666796701999200915144814 ◽

2020 ◽

Vol 01 ◽

Author(s):

Sonali Batra ◽

Sumit Sharma ◽

Payal Verma ◽

Nikhil Arora

Keyword(s):

Scientific Data ◽

Host Cells ◽

Angiotensin Converting Enzyme 2 ◽

The Third ◽

Precautionary Measures ◽

Severity Of The Disease ◽

Novel Coronavirus ◽

Diagnosis Of Infection ◽

Global Data ◽

Structural Aspects

Introduction: COVID-19 presents the global emergency in recent days and as a consequence the whole world is in a state of war. Continuous efforts by researchers are in process to establish sound scientific understanding regarding viral behavior and pathogenesis. Background: In recent days a lot of scientific data is published describing viral transfusion into host cells, comparing with SARS-CoV-1, viability of SARS-CoV-2, fatality and diagnosis of infection among infected patients. Thereby, motivating to take right decisions in order to treat and mitigate the COVID-19. Review results: Coronaviruses usually affect the respiratory tract and produce symptoms similar to pneumonia with varied complications. The spike protein on the surface of virus makes the SARS-CoV-2 phylogenetically different from other viruses of corona family. SARS-CoV-2 has an affinity for angiotensin converting enzyme-2 receptors present on human cells. The fatality of the disease is found to be low but the severity of the disease might vary from person to person. The incubation period is 14 days but the symptoms like dry cough and high fever are evident around 3-7 days. Already known anti inflammatory, immunomodulators and antiviral drugs are being tested and still under clinical trials. Conclusion: In this review, we are providing an insight over emergence, correlation with SARS-CoV-1 and interpretation of global data representing the severity of unexpected danger on humanity. Certain structural aspects and studies determining the viability of novel coronavirus have also been described. Moreover, case studies of recovered infected patients from COVID-19 explain the progression and patients pathophysiological conditions while suffering from infection. Clinical significance: There are many current strategies which are being tried and practiced to overcome this pandemic disease apart from precautionary measures. Although now, some decline has been seen, but the question still remain same standstill of whether the scientists are approaching towards the clinical solution, or still in midstream. This requires more study and intensive research to finally come to a concrete conclusion.

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CHILDREN IN CORONAVIRUSES’ WONDERLAND: WHAT CLINICIANS NEED TO KNOW

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2020.042 ◽

2020 ◽

Vol 12 (1) ◽

pp. e2020042

Author(s):

Giuseppe Lassandro ◽

Valentina Palladino ◽

Anna Amoruso ◽

Viviana Palmieri ◽

Giovanna Russo ◽

...

Keyword(s):

Respiratory Infections ◽

Multiorgan Failure ◽

Clinical Manifestations ◽

Severe Pneumonia ◽

Signs And Symptoms ◽

Upper Respiratory Tract ◽

Respiratory Tract Illnesses ◽

Life Threatening ◽

Human Coronaviruses ◽

Coronavirus Infections

Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans, (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults they may cause severe pneumonia that evolve in distress respiratory syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children such as infants, adolescents or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.

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Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Molecules ◽

10.3390/molecules25173980 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3980 ◽

Cited By ~ 4

Author(s):

Muchtaridi Muchtaridi ◽

M. Fauzi ◽

Nur Kusaira Khairul Ikram ◽

Amirah Mohd Gazzali ◽

Habibah A. Wahab

Keyword(s):

Angiotensin Converting Enzyme ◽

Host Cells ◽

Angiotensin Converting Enzyme Inhibition ◽

Converting Enzyme ◽

Mortality And Morbidity ◽

Angiotensin Converting Enzyme 2 ◽

Arterial Blood ◽

Potential Efficacy ◽

Novel Coronavirus

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

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Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival, and Six-Month Sequelae in COVID-19 Symptomatic Patients

Viruses ◽

10.3390/v13020281 ◽

2021 ◽

Vol 13 (2) ◽

pp. 281

Author(s):

Mattia Trunfio ◽

Francesco Venuti ◽

Francesca Alladio ◽

Bianca Maria Longo ◽

Elisa Burdino ◽

...

Keyword(s):

Disease Severity ◽

Clinical Manifestations ◽

Signs And Symptoms ◽

Predictive Marker ◽

Threshold Value ◽

Nasopharyngeal Swab ◽

Cycle Threshold ◽

Composite Scale ◽

Group B ◽

Novel Coronavirus

To date, there is no severe acute respiratory syndrome coronavirus 2-(SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤ 20.0, 20.0 < group B ≤ 28.0, and Group C > 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C; 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p < 0.01), and presence of six-month sequelae (p < 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.

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The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach

Scientific Reports ◽

10.1038/s41598-022-04778-y ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Alireza Mansouri ◽

Rasoul Kowsar ◽

Mostafa Zakariazadeh ◽

Hassan Hakimi ◽

Akio Miyamoto

Keyword(s):

Active Site ◽

Clinical Investigation ◽

Host Cells ◽

Spike Protein ◽

Angiotensin Converting Enzyme 2 ◽

Risk Of Death ◽

Main Protease ◽

Computational Data ◽

Novel Coronavirus ◽

The Impact

AbstractThe novel coronavirus disease (COVID-19) is currently a big concern around the world. Recent reports show that the disease severity and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. In addition, some steroid structures have been reported to affect coronavirus, SARS-CoV-2, function and activity. The entry of SARS-CoV-2 into host cells depends on the binding of coronavirus spike protein to angiotensin converting enzyme-2 (ACE2). Viral main protease is essential for the replication of SARS-CoV-2. It was hypothesized that steroid molecules (e.g., estradiol, progesterone, testosterone, dexamethasone, hydrocortisone, prednisone and calcitriol) could occupy the active site of the protease and could alter the interaction of spike protein with ACE2. Computational data showed that estradiol interacted more strongly with the main protease active site. In the presence of calcitriol, the binding energy of the spike protein to ACE2 was increased, and transferring Apo to Locked S conformer of spike trimer was facilitated. Together, the interaction between spike protein and ACE2 can be disrupted by calcitriol. Potential use of estradiol and calcitriol to reduce virus invasion and replication needs clinical investigation.

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Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

10.1101/2020.05.07.083147 ◽

2020 ◽

Cited By ~ 4

Author(s):

Sanchita Hati ◽

Sudeep Bhattacharyya

Keyword(s):

Angiotensin Converting Enzyme ◽

Binding Affinity ◽

Disulfide Bonds ◽

Host Cells ◽

Converting Enzyme ◽

Dynamic Simulations ◽

Angiotensin Converting Enzyme 2 ◽

Novel Coronavirus ◽

The Impact ◽

Spike Proteins

AbstractThe novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.

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