scholarly journals Elucidating the differences in the molecular mechanism of receptor binding between 2019-nCoV and the SARS-CoV viruses using computational tools

2020 ◽  
Author(s):  
Hien T. T. Lai ◽  
Ly H. Nguyen ◽  
Agata Kranjc ◽  
Toan T. Nguyen ◽  
Duc Nguyen-Manh
Keyword(s):  
Receptor Binding ◽  
Elderly Population ◽  
Hydrophobic Interactions ◽  
Viral Disease ◽  
World Health ◽  
Pharmacological Intervention ◽  
Computational Tools ◽  
Viral Genomes ◽  
Binding Interface ◽  
Health Organization

AbstractThe outbreak of the 2019-nCoV coronavirus causing severe acute respiratory syndrome which can be fatal, especially in elderly population, has been declared a pandemic by the World Health Organization. Many biotechnology laboratories are rushing to develop therapeutic antibodies and antiviral drugs for treatment of this viral disease. The viral CoV spike (S) glycoprotein is one of the main targets for pharmacological intervention. Its receptor-binding domain (RBD) interacts with the human ACE2 receptor ensuring the entry of the viral genomes into the host cell. In this work, we report on the differences in the binding of the RBD of the previous coronavirus SARS-CoV and of the newer 2019-nCoV coronavirus to the human ACE2 receptor using atomistic molecular dynamics techniques. Our results show major mutations in the 2019-nCoV RBD with respect to the SARS-CoV RBD occurring at the interface of RBD-ACE2 complex. These mutations make the 2019-nCoV RBD protein backbone much more flexible, hydrophobic interactions are reduced and additional polar/charged residues appear at the interface. We observe that higher flexibility of the 2019-nCoV RBD with respect to the SARS-CoV RBD leads to a bigger binding interface between the 2019-nCoV RBD and ACE2 and to about 20% more contacts between them in comparison with SARS-CoV. Taken together, the 2019-nCoV RBD shows more stable binding interface and higher binding affinity for the ACE2 receptor. The mutations not only stabilize the binding interface, they also lead to overall more stable 2019-nCoV RBD protein structure, even far from the binding interface. Our results on the molecular differences in the binding between the two viruses can provide important inputs for development of appropriate antiviral treatments of the new viruses, addressing the necessity of ongoing pandemics.

scholarly journals Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

2019 ◽  
Author(s):  
Petter I. Andersen ◽  
Klara Krpina ◽  
Aleksandr Ianevski ◽  
Nastassia Shtaida ◽  
Eunji Jo ◽  
...  
Keyword(s):  
Influenza A ◽  
Rift Valley Fever Virus ◽  
Antiviral Agents ◽  
Viral Disease ◽  
World Health ◽  
Valley Fever ◽  
The World ◽  
Health Organization ◽  
Hiv 1

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

scholarly journals Characteristics of geriatric neurology patients treated at the central hospital of Sanglah Denpasar in 2019

2020 ◽  
Vol 7 (2) ◽  
pp. 245
Author(s):  
Stephanie Elizabeth Gunawan ◽  
Anak Agung Ayu Putri Laksmidewi
Keyword(s):  
Medical Records ◽  
Elderly Population ◽  
Neurological Diseases ◽  
Head Injuries ◽  
Elderly Person ◽  
The Elderly ◽  
World Health ◽  
Central Hospital ◽  
The World ◽  
Health Organization

Background: According to the World Health Organization (WHO), an elderly person is someone who has entered the age of 60 years and above whose percentage tends to increase along with decreasing morbidity of the elderly. Geriatric Neurology itself is the study of a group of neurological diseases in the elderly. Based on 2012 data, the proportion of elderly population in Indonesia is 7.59%. This is accompanied by an increase in the dependency ratio of the productive age population to the non-productive age population. The results of the 2013 Basic Health Research showed an increase in the prevalence of neurological disease in the elderly which was the main cause of death in 15 regencies in 2011. It is to find out the 5 most neurological diseases in the elderly, clinical characteristics and outcomes of geriatric neurology patients treated at the Central Hospital of Sanglah.Methods: It is a retrospective study using no control by looking at medical records in geriatric neurology patients aged 60 years and over who visited the Central Hospital of Sanglah in the March to May 2019 period.Results: A total of 200 patients consisted of 111 men (55.5%) and 89 women (44.5%) who were divided into 5 most geriatric neurology diseases which included 1. ischemic stroke, 2. bleeding stroke, 3. brain tumor, 4. injury head, and 5. epilepsy. The number of deaths was 16, of which 7 cases were caused by sepsis and pneumonia.Conclusions: Stroke, tumors, head injuries and epilepsy are the dominant neurological diseases found. The focus of care and supervision of elderly neurology patients is expected to be further enhanced to prevent side effects that will extend the patient’s treatment period in the hospital which will automatically increase the burden on the hospital itself.

scholarly journals COVID-19 Pandemic: A Global Disaster

2021 ◽  
Vol 1 (1) ◽  
pp. 7-8
Author(s):  
Solomon Arigwe Joseph ◽  
Abuhuraira Ado Musa ◽  
Faisal Muhammad ◽  
Tijjani Muhammad Ahmad
Keyword(s):  
Public Health ◽  
World Health Organization ◽  
Signs And Symptoms ◽  
Viral Disease ◽  
Hubei Province ◽  
Public Health Emergency ◽  
World Health ◽  
Novel Coronavirus ◽  
Health Organization

People began to become ill in late December 2019 in Wuhan, Hubei Province, China, and the illness was revealed to be a kind of pneumonia with unusual signs and symptoms. It was eventually discovered as a novel coronavirus, a virus that causes widespread sickness in animals and birds. World Health Organization (WHO) named this new viral disease coronavirus disease 2019 (COVID-19) and declared a Public Health Emergency of International Concern in January 2020.

scholarly journals The expression of hACE2 receptor protein and its involvement in SARS-CoV-2 entry, pathogenesis, and its application as potential therapeutic target

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 177-196
Author(s):  
Lobna Al-Zaidan ◽  
Sarra Mestiri ◽  
Afsheen Raza ◽  
Maysaloun Merhi ◽  
Varghese Philipose Inchakalody ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Virus Disease ◽  
Respiratory Illness ◽  
Host Cells ◽  
World Health ◽  
Receptor Protein ◽  
Unknown Etiology ◽  
Spike Glycoprotein ◽  
Binding Interface

Pneumonia cases of unknown etiology in Wuhan, Hubei province, China were reported to the World Health Organization on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Corona virus disease 2019 (COVID-19). The disease outspread was followed by WHO declaration of COVID-19 pandemic as a “Public Health Emergency of International Concern”. SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender, and underlying comorbidities. Infection initiates when viral particles bind to the host cell surface receptors where SARS-CoV-2 spike glycoprotein subunit 1 binds to the Angiotensin Converting Enzyme 2 (ACE2). It is of importance to mention that SARS-CoV and SARS-CoV-2 viruses’ mediate entry into the host cells via ACE2 receptor which might be correlated with the structural similarity of spike glycoprotein subunit 1 of both SARS viruses. However, the structural binding differs, whereas ACE2 receptor binding affinity with SARS-CoV-2 is 4 folds higher than that with SARS-CoV. Moreover, amino acids sequence divergence between the two S glycoproteins might be responsible for differential modulations of the specific immune response to both viruses. Identification of different aspects such as binding affinity, differential antigenic profiles of S-glycoproteins, and ACE2 mutations might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. In this review, we aim to elaborate on the expression of hACE2 receptor protein and its binding with SARS-CoV-2 S1 subunit, the possible immunogenic sequences of spike protein, effect of ACE 2 polymorphism on viral binding, and infectivity/susceptibility to disease. Furthermore, targeting of hACE2 receptor binding with SARS-CoV-2 S1 subunit via various mechanisms will be discussed to understand its role in therapeutics.

Impact of Tuberculosis in Elderly Population

2018 ◽  
pp. 326-338
Author(s):  
Gagan Chooramani ◽  
Pooja Singh
Keyword(s):  
Clinical Characteristics ◽  
Elderly Population ◽  
The Elderly ◽  
World Health ◽  
Tuberculosis Patients ◽  
Disease Outcomes ◽  
Age Related ◽  
Health Organization ◽  
The Impact ◽  
Poor Memory

The World Health Organization has declared that the spread of tuberculosis is a global emergency. Despite the implementation of strong tuberculosis-control initiatives by WHO, this highly infectious disease continues to affect all vulnerable populations, including the elderly population. Adverse social factors and poor living conditions also affect the elderly much more than the young. The clinical characteristics of tuberculosis in older adults can be unusual and may be confused with age-related illnesses. Various factors related to old age can also cause complications in the diagnosis, treatment, and disease outcomes for tuberculosis patients. The contributory factors may be poor memory, deafness, mental confusion, or impairment of speech. In addition, therapy for tuberculosis in elderly individuals is challenging because of the increased incidence of adverse drug reactions. Hence, understanding the impact of these substantial aspects will help to overcome the problem of tuberculosis in the elderly population.

scholarly journals The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection

2020 ◽  
Vol 21 (4) ◽  
pp. 1511 ◽  
Author(s):  
Nícia Rosário-Ferreira ◽  
António J. Preto ◽  
Rita Melo ◽  
Irina S. Moreira ◽  
Rui M. M. Brito
Keyword(s):  
Viral Disease ◽  
Influenza Viruses ◽  
World Health ◽  
World Population ◽  
Structural Protein ◽  
Human Respiratory Tract ◽  
Host Interactions ◽  
The World ◽  
Health Organization

Influenza (flu) is a contagious viral disease, which targets the human respiratory tract and spreads throughout the world each year. Every year, influenza infects around 10% of the world population and between 290,000 and 650,000 people die from it according to the World Health Organization (WHO). Influenza viruses belong to the Orthomyxoviridae family and have a negative sense eight-segment single-stranded RNA genome that encodes 11 different proteins. The only control over influenza seasonal epidemic outbreaks around the world are vaccines, annually updated according to viral strains in circulation, but, because of high rates of mutation and recurrent genetic assortment, new viral strains of influenza are constantly emerging, increasing the likelihood of pandemics. Vaccination effectiveness is limited, calling for new preventive and therapeutic approaches and a better understanding of the virus–host interactions. In particular, grasping the role of influenza non-structural protein 1 (NS1) and related known interactions in the host cell is pivotal to better understand the mechanisms of virus infection and replication, and thus propose more effective antiviral approaches. In this review, we assess the structure of NS1, its dynamics, and multiple functions and interactions, to highlight the central role of this protein in viral biology and its potential use as an effective therapeutic target to tackle seasonal and pandemic influenza.

scholarly journals Obstetrics and gynaecology in the era of COVID-19

2020 ◽  
Vol 9 (11) ◽  
pp. 4777
Author(s):  
Angela Mary George ◽  
Daniel Manoj ◽  
Sowmya Ramani ◽  
Lalropuii . ◽  
Murugan Timiri Palani ◽  
...  
Keyword(s):  
Women’S Health ◽  
Women's Health ◽  
Psychosocial Support ◽  
Viral Disease ◽  
World Health ◽  
Significant Morbidity ◽  
Obstetrics And Gynaecology ◽  
Global Pandemic ◽  
The World ◽  
Health Organization

The World Health Organization has declared the outbreak of COVID-19 as a global pandemic. The alarming levels of spread and severity of the viral disease has resulted in significant morbidity and mortality. Women often face the highest risk of suffering devastating losses from the pandemic. Historically, women’s health has always been inadequately represented in responses to global outbreaks. Resources are often funnelled away from women’s health services towards targets perceived to be more important. Pregnant women with suspected, probable or confirmed COVID-19, should have access to obstetric and foetal medicine, neonatal care as well as mental health and psychosocial support, at facilities ready to tackle maternal and neonatal complications. In this article, we attempt to look at the challenges faced by gynaecologists because of this pandemic, and provide an overview on the current protocols in antenatal care, foetal care, childbirth, and oncological care.

scholarly journals The state of psychogeriatrics in Europe: challenges and opportunities in six European countries

2014 ◽  
Vol 27 (8) ◽  
pp. 1243-1246 ◽  
Author(s):  
Lia Fernandes ◽  
Raimundo Mateos ◽  
Knut Engedal ◽  
Armin von Gunten ◽  
Max L. Stek ◽  
...  
Keyword(s):  
World Health Organization ◽  
Elderly Population ◽  
The Elderly ◽  
World Health ◽  
Know How ◽  
Challenges And Opportunities ◽  
To Come ◽  
New Policies ◽  
Health Organization ◽  
National Governments

With the increase in aging all over the world, and the elderly population nearly tripling from 524 million (8% of the world's population) in 2010 to 1.5 billion (16% of the world's population) in 2050, we will face new challenges and opportunities in providing healthcare. In 2050, it is estimated that Europe will see an increase of 70% in elderly population aged over 65 years, and 170% in those aged over 80 years (World Health Organization (WHO), 2011). It is vital to respond to the needs of this emerging population and the consequent rise in chronic diseases, especially dementia and mental health disorders, which will overload the healthcare system, as well as raise health and social costs, and demand new policies from national governments (World Health Organization, 2012). We urgently need to know how to organize healthcare for elderly people in the years to come.

scholarly journals Influenza in Brazil: surveillance pathways

2016 ◽  
Vol 10 (01) ◽  
pp. 13-23 ◽  
Author(s):  
Ligia Cantarino ◽  
Edgar Merchan-Hamann
Keyword(s):  
Preventive Measure ◽  
Viral Disease ◽  
World Health ◽  
Influenza Surveillance ◽  
Surveillance Systems ◽  
Health Authorities ◽  
Model Set ◽  
Health Organization ◽  
Worldwide Network

Influenza is a viral disease of global concern that has demanded the attention of health authorities. Since 1947, as a preventive measure, the World Health Organization monitors viral circulation to define the annual vaccine through a worldwide network of laboratories. This article presents the structuring of influenza surveillance in Brazil and highlights virological surveillance and the role of diagnostic laboratories as well as the expansion of actions to improve detection and expedite responses. The model set corresponds to sentinel surveillance complemented by the universal notification of severe acute respiratory syndrome investigating outbreaks, deaths, and unusual events and monitoring hospitalization and mortality in an expanded surveillance. In this review, we address aspects of influenza surveillance in animals, the need for interagency integration, and the sharing of information in many surveillance systems.

scholarly journals Potential activity of a selected natural compounds on SARS-CoV-2 RNA-dependent-RNA polymerase, and binding affinity of the receptor-binding domain (RBD)

2020 ◽  
Author(s):  
Hisham Altayeb ◽  
Lamjed Bouslama ◽  
Jawaher Abdualbaqi Abdulhakimc ◽  
Kamel Chaieb ◽  
Othman A. S. Baothman ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Receptor Binding ◽  
Natural Compounds ◽  
Binding Domain ◽  
World Health ◽  
Receptor Binding Domain ◽  
Global Public Health ◽  
Pheophorbide A ◽  
Rna Dependent Rna Polymerase ◽  
Health Organization

Abstract Coronavirus disease (COVID-19) is caused by SARS-CoV-2 and represents the causative agent of a potentially lethal disease. COVID-19 has been described as a significant global public health pandemic by the World Health Organization due to its high mortality rate, rapid spread, and the lack of drugs and vaccines for it. Active antiviral drugs are desperately needed to combat the potential return of severe acute respiratory syndrome (SARS).In this study, we selected 39 natural compounds present in plants, algae, and sponges with antiviral activity. Molecular docking was used to screen the compounds’ activity on SARS- CoV-2 RNA-dependent-RNA polymerase, receptor-binding domain (RBD), and the human ACE2 receptor. Compounds with binding energy ≤ -6.5 kcal/mol enter pre-clinical testing using in silco ADME/Tox (absorption, distribution, metabolism, excretion, and toxicity).We found eight potential SARS-CoV-2 inhibitors: (glycyrrhizin, rutin, baicalin, 1, 6-di-O- galloyl-beta-D-glucose, pyropheophorbide A, pheophorbide A, beta-Sitosterol, and vitexin). These outcomes indicate that these compounds could be potential candidates to be utilized in lead optimization for the design and production of the anti-SARS-CoV-2 drug.

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