Quantum biochemical analysis of the binding interactions between a potential inhibitory drug and the Ebola viral glycoprotein.

Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.Communicated by Ramaswamy H. Sarma.

Preparedness Tested: Severe Cerebral Malaria Presenting as a High-Risk Person Under Investigation for Ebola Virus Disease at a US Hospital.

In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a "wet" person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.

Ebola virus disease: An emerging and re-emerging viral threat.

The genus Ebolavirus from the family Filoviridae is composed of five species including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40) and an RNA dependent RNA polymerase. These viruses have become a global health concern because of mortality, their rapid dissemination, new outbreaks in West-Africa, and the emergence of a new condition known as "Post-Ebola virus disease syndrome" that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are many gaps in the understanding of the mechanisms that may induce the development of such autoimmune-like syndromes. Some of these mechanisms may include a high formation of neutrophil extracellular traps, an uncontrolled "cytokine storm", and the possible formation of auto-antibodies. The likely appearance of autoimmune phenomena in Ebola survivors suppose a new challenge in the management and control of this disease and opens a new field of research in a special subgroup of patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and treatment of Ebola virus disease are reviewed and some strategies for control of disease are discussed.

Caracterización clínico epidemiológica de pacientes con ébola en un centro de tratamiento de Sierra Leona / Clinical-epidemiological characterization of Ebola disease in patients at a treatment center in Sierra Leone

Introducción: La enfermedad del ébola se dio a conocer por primera vez en 1976, con una letalidad muy elevada en todos los brotes detectados. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes portadores de la enfermedad por el virus del Ébola. Métodos: Se realizó un estudio observacional, descriptivo y transversal en 424 pacientes ingresados en un centro de tratamiento de ébola en la República de Sierra Leona, África occidental, con el diagnóstico confirmado mediante la técnica de reacción en cadena de la polimerasa para virus Ébola, durante el período de noviembre de 2014 hasta marzo de 2015. Resultados: Se muestra que el grupo etario más afectado fue el de 25 a 34 con un 25,9 por ciento. La mayor letalidad se presentó en los pacientes con más de 65 años de edad con un 44,4 por ciento. El síntoma que prevaleció fue la fiebre para un 61,8 por ciento, y el hipo se presentó en el 88,8 por ciento de los fallecidos. Conclusión: Se concluye que la enfermedad no tuvo distinción significativa con el sexo. La mayor letalidad se presentó en las edades geriátricas. Los síntomas más frecuentes fueron la fiebre, diarrea y el decaimiento. El hipo fue el signo que más se presentó en los pacientes que fallecieron(AU)

Introduction: Ebola disease was first reported in 1976 with a very high lethality in all outbreaks. Objective: To clinically and epidemiologically characterize the patients carriers of Ebola virus disease. Methods: we conducted an observational, descriptive and cross-sectional study in 424 patients admitted to an Ebola Treatment Center in the Republic of Sierra Leone, West Africa from November 2014 to March 2015. The polymerase chain reaction technique for Ebola virus confirmed the diagnosis. Medical records provided all data. Results: The age group most affected was 25 to 34 (25.9 percent). The highest lethality occurred in those over 65 years of age (44.4 percent ). Fever was the prevailing symptom (61.8 percent) and hiccups occurred in 88.8 percent of the deceased. Conclusion: Clinical manifestations were variable, although fever was the main symptom. Hiccup was a sign of poor prognosis when associated with a higher percentage of mortality. Lethality was high(AU)

On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains.

The number of fatalities and economic losses caused by the Ebola virus infection across the planet culminated in the havoc that occurred between August and November 2014. However, little is known about the molecular protein profile of this devastating virus. This work represents a thorough bioinformatics analysis of the regularities of charge distribution (polar profiles) in two groups of proteins and their functional domains associated with Ebola virus disease: Ebola virus proteins and Human proteins interacting with Ebola virus. Our analysis reveals that a fragment exists in each of these proteins-one named the "functional domain"-with the polar profile similar to the polar profile of the protein that contains it. Each protein is formed by a group of short sub-sequences, where each fragment has a different and distinctive polar profile and where the polar profile between adjacent short sub-sequences changes orderly and gradually to coincide with the polar profile of the whole protein. When using the charge distribution as a metric, it was observed that it effectively discriminates the proteins from their functional domains. As a counterexample, the same test was applied to a set of synthetic proteins built for that purpose, revealing that any of the regularities reported here for the Ebola virus proteins and human proteins interacting with Ebola virus were not present in the synthetic proteins. Our results indicate that the polar profile of each protein studied and its corresponding functional domain are similar. Thus, when building each protein from its functional domai-adding one amino acid at a time and plotting each time its polar profile-it was observed that the resulting graphs can be divided into groups with similar polar profiles.

Clinical Features and Outcome of Ebola Virus Disease in Pediatric Patients: A Retrospective Case Series.

Clinical and outcome data on pediatric Ebola virus disease are limited. We report a case-series of 33 pediatric patients with Ebola virus disease in a single Ebola Treatment Center in 2014-2015. The case-fatality rate was 42%, with the majority of deaths occurring within 10 days of admission.

The Cuban Response to the Ebola Epidemic in West Africa: Lessons in Solidarity.

In December 2013 the first case of Ebola appeared in Guinea. In September 2014 the United Nations (UN) and its specialized agency the World Health Organization (WHO) issued a call for medical collaboration in response to the medical crisis and social disaster caused by the Ebola virus epidemic in West Africa. Cuban authorities responded immediately to the call by offering specialized help for the epidemic, in collaboration with WHO. A group of 256 Cuban doctors, nurses and other health professionals provided direct care during the Ebola epidemic in Sierra Leone, Liberia and Equatorial Guinea from October 2014 to April 2015. This paper explains the main features of the Cuban health system, describes the development of Cuba's international medical cooperation approach, and highlights the work done by Cuban health collaborators in addressing the damage caused by the Ebola epidemic. Information used includes reports and documents of the Ministry of Public Health of Cuba, reports of WHO and PAHO, and articles published in scientific journals and newspaper articles. The response of the Cuban medical teams to the Ebola epidemic in West Africa is only one example of the Cuban efforts to strengthening health care provision in areas of need throughout the world.

Avances científicos en las estrategias terapéuticas contra la enfermedad por virus del ébola / Scientific advances in therapeutic strategies against disease by ebola virus

La enfermedad por el virus del Ébola se conoce desde hace treinta años como mortal, contagiosa y de difícil diagnóstico y tratamiento. Numerosos estudios se han realizado para comprender la patogénesis del virus y con ello los posibles tratamientos que puedan generar control de la enfermedad. Sin embargo, no hay hasta la fecha un fármaco o vacuna con licencia para combatir el virus del Ébola. El tratamiento está basado solo en aliviar los síntomas y prevenir el contagio por medio de acciones que ayuden a minimizar el riesgo de infección. En esta revisión, se presentan las diferentes perspectivas del estado actual de la investigación sobre fármacos antivirales y vacunas en fases de desarrollo para la infección del virus del Ébola.

Ebola virus disease has been known for thirty years as a lethal, contagious and difficult to diagnose and treat disease. Numerous studies have been conducted to understand the pathogenesis of the virus and thus the possible treatments that may promote disease control. However, to date there is no licensed vaccine or medicine to fight Ebola virus. The treatment is based only on relieving symptoms and preventing contagion through actions that help minimize the risk of infection. This review presents different perspectives of the current state of research on antiviral medicine and vaccines in development stages for Ebola virus infection.

Ebola virus disease and the search for a cure

Ebola virus disease (EVD) was first identified in 1976 in Yambuku, Zaire (now the Democratic Republic of Congo), and is caused by an RNA virus in the filovirus family (Feldmann & Geisbert). The current strain circulation in West Africa is very similar to the original strain (>95% homology). The origin of the current outbreak remains unknown, but it is suspected to be from an animal reservoir with intermediary species (Fauci). Randomized clinical trials with adaptive design are ongoing to evaluate potential new therapies for EVD...