scholarly journals Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yuefei Jin ◽  
Wangquan Ji ◽  
Haiyan Yang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Endothelial Activation ◽  
World Health ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapeutic Implications ◽  
Endothelial Inflammation ◽  
The World ◽  
Health Organization

AbstractOn 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization. As of 4 August 2020, more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients. Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation. Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier, promoting pro-coagulative state, inducing endothelial inflammation, and even mediating leukocyte infiltration. This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said
Keyword(s):  
Medicinal Plants ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Treatment Protocol ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Promising Source

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.

scholarly journals Virtual Screening of Naturally Occurring Antiviral Molecules for SARS-CoV-2 Mitigation Using Docking Tool on Multiple Molecular Targets

2020 ◽  
Author(s):  
Shiwani Rana ◽  
Sanjay Sharma ◽  
Kalyan Sundar Ghosh
Keyword(s):  
Molecular Targets ◽  
World Health ◽  
Huge Number ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Naturally Occurring ◽  
The World ◽  
Docking Tool ◽  
Health Organization ◽  
3Cl Protease

<p>The coronavirus catastrophe (COVID-19) caused by a novel strain of coronavirus (SARS-CoV-2) has turned the world upside down at an unprecedented level and has been declared as a pandemic by World Health Organization (WHO). It has resulted huge number of fatalities and infections due to the severe lower respiratory tract sickness in the infected people. Research across the world is in progress to identify inhibitors against various molecular targets associated with this viral infection. Among these targets, a very important one is a cysteine like protease or 3CL protease (3CLpro) and that is required for the replication of the virus. In the present study, initially we have investigated the potential of twenty naturally occurring antiviral molecules to function as inhibitors against the activity of main viral protease (3CLpro) so as to put a halt on viral replication. The investigation has been carried out through docking of the molecules with 3CLpro. Based on the results, three most potential molecules (bilobetin, ginkgetin and sciadopitysin) have been screened. Further these molecules were subjected for checking their activity on other molecular targets like a papain like protease (PLpro), spike protein S1, RNA dependent RNA polymerase (RdRp), angiotensin converting enzyme 2 (ACE2) receptor. In addition to 3CLpro inhibition, ginkgetin was predicted as an inhibitor of PLpro also. But none of these three compounds was found effective on rest other molecular targets. </p>

scholarly journals Fully Human Antibody Immunoglobulin from Transchromosomic Bovines is Potent Against SARS-CoV-2 Variant Pseudoviruses

2021 ◽  
Author(s):  
Thomas Luke ◽  
Hua Wu ◽  
Kristi A Egland ◽  
Eddie J Sullivan ◽  
Christoph L Bausch
Keyword(s):  
293T Cell ◽  
Spike Protein ◽  
World Health ◽  
Human Antibody ◽  
Phase 2 ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Health Organization ◽  
Transmembrane Serine Protease ◽  
Multiple Variants

SAB-185 is a fully human polyclonal anti-SARS-CoV-2 immunoglobulin produced from the plasma of transchromosomic bovines that are hyperimmunized with recombinant SARS-CoV-2 Wuhan-Hu-1 Spike protein. SAB-185 is being evaluated for efficacy in an adaptive phase 2/3 clinical trial. The World Health Organization (WHO) has identified multiple Variants-of-Concern and Variants-of-Interest (VOC/VOI) that have mutations in their Spike protein that appear to increase transmissibility and/or reduce the effectiveness of therapeutics and vaccines, among other parameters of concern. SAB-185 was evaluated using a lentiviral-based pseudovirus assay performed in a BSL2 environment that incorporates a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The results indicate that SAB-185 retained neutralization potency against multiple SARS-CoV-2 pseudovirus variants, including the Delta, Kappa and Lambda variants, that are supplanting other VOC/VOI in many countries and regions around the world.

scholarly journals Actual antihistamine therapy

2020 ◽  
pp. 26-35
Author(s):  
D. V. Shabanov ◽  
Ju. E. Lutkovskaya
Keyword(s):  
Allergic Rhinitis ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
World Health ◽  
Asian Studies ◽  
Inflammatory Reactions ◽  
Medical Specialists ◽  
The World ◽  
Health Organization ◽  
Allergy Symptom

The significance of the issues of allergic diseases is not in doubt. It is difficult to find a person who has not suffered at least some Allergy symptom, not everyone develops diseases, but most people face Allergy symptoms. The prevalence of various allergic diseases is increasing every year, currently reaching 30% of the population, and the world health organization predicts it will reach 50% in the next few decades. The most common nosologies are allergic rhinitis, bronchial asthma, atopic dermatitis, urticaria, but there are many other conditions of hypersensitivity. This article addresses the issues of inflammatory reactions in General and specifically allergic inflammation, discusses the main aspects of the pathogenesis of allergic rhinitis and urticaria, and questions of drug therapy for these diseases. Most people are sure that they can take anti-allergic medications for allergies, and most often they are referring to antihistamines. Unfortunately, even some medical specialists lack an understanding of the specifics of antihistamine therapy. some people still believe that there are three or four generations of antihistamines, and patients use drugs not as prescribed by doctors, but on the recommendation of friends or pharmacists. Irrational use of antihistamines leads to a decrease in effectiveness, and it is not uncommon to discredit specific drugs and groups of drugs in General. This article demonstrates the results of various European and Asian studies on the effectiveness and safety of antihistamines and bilastin in particular, as well as their own experience of using antihistamines in practice.

scholarly journals Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

2021 ◽  
Author(s):  
Tue W. Kragstrup ◽  
Helene Søgaard Singh ◽  
Ida Grundberg ◽  
Ane Langkilde-Lauesen Nielsen ◽  
Felice Rivellese ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Disease ◽  
Kidney Disease ◽  
Severe Acute Respiratory Syndrome ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Baseline Levels ◽  
Health Organization

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). COVID-19 is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome and death. Methods This study used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 outcomes scale. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. Findings High baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 in plasma from COVID-19 patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 in plasma from COVID-19 patients with hypertension were significantly higher compared to patients without hypertension (P = 0.0045). The plasma ACE2 levels were also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 levels comparing patients with or without pre-existing lung disease, diabetes, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 and worse WHOmax category during 28 days were more pronounced in COVID-19 positive patients compared with COVID-19 negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 levels could be a link between severe COVID-19 disease and its risk factors, namely hypertension, pre-existing heart disease and pre-existing kidney disease. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 and ACE1 activity. This is interesting because ACE1 (serum ACE) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19. Key Points Question Can plasma levels of the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2), predict outcome of coronavirus disease of 2019 (COVID-19). Findings In this study of 306 COVID-19 positive patients, high baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse outcome measured by the World Health Organization (WHO) COVID-19 outcomes scale. Meaning Measuring ACE2 is potentially valuable in predicting COVID-19 outcomes and link COVID-19 disease and the risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

scholarly journals Virtual Screening of Naturally Occurring Antiviral Molecules for SARS-CoV-2 Mitigation Using Docking Tool on Multiple Molecular Targets

2020 ◽  
Author(s):  
Shiwani Rana ◽  
Sanjay Sharma ◽  
Kalyan Sundar Ghosh
Keyword(s):  
Molecular Targets ◽  
World Health ◽  
Huge Number ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Naturally Occurring ◽  
The World ◽  
Docking Tool ◽  
Health Organization ◽  
3Cl Protease

<p>The coronavirus catastrophe (COVID-19) caused by a novel strain of coronavirus (SARS-CoV-2) has turned the world upside down at an unprecedented level and has been declared as a pandemic by World Health Organization (WHO). It has resulted huge number of fatalities and infections due to the severe lower respiratory tract sickness in the infected people. Research across the world is in progress to identify inhibitors against various molecular targets associated with this viral infection. Among these targets, a very important one is a cysteine like protease or 3CL protease (3CLpro) and that is required for the replication of the virus. In the present study, initially we have investigated the potential of twenty naturally occurring antiviral molecules to function as inhibitors against the activity of main viral protease (3CLpro) so as to put a halt on viral replication. The investigation has been carried out through docking of the molecules with 3CLpro. Based on the results, three most potential molecules (bilobetin, ginkgetin and sciadopitysin) have been screened. Further these molecules were subjected for checking their activity on other molecular targets like a papain like protease (PLpro), spike protein S1, RNA dependent RNA polymerase (RdRp), angiotensin converting enzyme 2 (ACE2) receptor. In addition to 3CLpro inhibition, ginkgetin was predicted as an inhibitor of PLpro also. But none of these three compounds was found effective on rest other molecular targets. </p>

Recent Advances in Discovery of Potent Proteases Inhibitors Targeting the SARS Coronaviruses

2020 ◽  
Vol 20 ◽  
Author(s):  
Arti Sharma ◽  
Kajal Kaliya ◽  
Sushil K. Maurya
Keyword(s):  
Global Health ◽  
Natural Product ◽  
World Health ◽  
Fatality Rate ◽  
Therapeutic Approaches ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Recent Advances ◽  
The World ◽  
Health Organization

: Across the globe, countries are being challenged by the SARS-CoV-2 (COVID-19) pandemic in ways they have never been before. Global outbreak of SARS-CoV-2 with an uncertain fatality rate has imposed extreme challenges on global health. The World Health Organization (WHO) has officially declared the outbreak of COVID-19 a pandemic, after the disease caused by the new coronavirus spread to more than 100 countries. To date, various therapeutic approaches has been proposed and are being implemented to combat this pandemic, but unfortunately, no sovereign remedy has been es-tablished yet. Protease enzymes are important targets to develop therapies for the treatment of infections caused by SARS coronaviruses. In this review, an overview is given on recent advances in discovery of potent protease inhibitors targeting the SARS coronaviruses. Different classes of natural product inhibitors targeting protease enzymes of SARS coronaviruses have been studied in detail along with their structure activity relationship analysis. This study emphasized on important covalent and non-covalent small molecule inhibitors which effectively inhibited chymotrypsin-like cysteine protease (3CLpro) and papain-like protease (PLpro) of two SARS coronaviruses i.e. SARS-CoV-1 and SARS-CoV-2. Repurposing of drugs has been also outlined in this study to understand their roles as quick-to-be-identified therapy to combat these zoonotic coronaviruses.

scholarly journals AXL, an Important Host Factor for DENV and ZIKV Replication

2021 ◽  
Vol 11 ◽  
Author(s):  
Shengda Xie ◽  
Huiru Zhang ◽  
Zhenjie Liang ◽  
Xingmiao Yang ◽  
Ruibing Cao
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Infection Process ◽  
Host Factors ◽  
Host Cells ◽  
World Health ◽  
Enveloped Viruses ◽  
The World ◽  
Important Host ◽  
Health Organization

Flaviviruses, as critically important pathogens, are still major public health problems all over the world. For instance, the evolution of ZIKV led to large-scale outbreaks in the Yap island in 2007. DENV was considered by the World Health Organization (WHO) as one of the 10 threats to global health in 2019. Enveloped viruses hijack a variety of host factors to complete its replication cycle. Phosphatidylserine (PS) receptor, AXL, is considered to be a candidate receptor for flavivirus invasion. In this review, we discuss the molecular structure of ZIKV and DENV, and how they interact with AXL to successfully invade host cells. A more comprehensive understanding of the molecular mechanisms of flavivirus-AXL interaction will provide crucial insights into the virus infection process and the development of anti-flavivirus therapeutics.

scholarly journals Acute Leukemia of Ambiguous Lineage with a Rare Abnormality Del17p by FISH Analysis

2020 ◽  
Vol 5 (2) ◽  
pp. 79-82
Author(s):  
Naeem Abbas ◽  
◽  
Samra Waheed ◽  
Aisha Jamal ◽  
Ali Saleem ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
World Health ◽  
Fish Analysis ◽  
Rare Entity ◽  
Therapeutic Approaches ◽  
The World ◽  
Health Organization ◽  
Acute Myeloid

Abstract: The World Health Organization (WHO) has categorized acute undifferentiated leukemia (AUL) as a rare subtype of acute leukemia of ambiguous lineage (ALAL). The prognosis of AUL is considered poor and it expresses no known lineage-specific markers. In majority of the cases, AUL has been associated with karyotypic abnormalities, most commonly deletion 5q and complex karyotype. Deletion 17p correlation with acute myeloid leukemia and myelodysplastic syndome has been previously established and is associated with poorer outcomes. Herein we are reporting a case of forty years old male who was referred to National institute of blood diseases and bone marrow transplantation with complains of fever, multiple neck swellings, and early satiety and was diagnosed as Acute Undifferentiated Leukemia along with deletion 17p. This is a rare entity and can aid in further diagnostic and therapeutic approaches. Keywords: Acute undifferentiated leukemia, Deletion 17p, Flourescnece in situ hybridization, Allogeneic haematopoetic stem cell transplantation, Flow cytometry.

Sign in / Sign up

Export Citation Format

Share Document