Recent advances in the discovery and development of Ebola virus inhibitors / 药学学报

Ebola virus is extremely virulent and highly contagious. Ebola virus causes outbreaks of severe hemorrhagic fever, with human mortality rates of up to 90%. There is currently no preventive or therapeutic treatment in the form of vaccines, biological or small molecular agents. Currently, a lot of anti-Ebola virus agents have been reported. Here, we review the latest advances in this field.

Establishment of a new genus of filovirus (Mengla virus) entry evaluating system and entry inhibitors discovery / 药学学报

Mengla virus (MLAV), isolated from the bats in China, was identified as a new genus of filovirus in 2019, i.e. Dianlovirus genus of Filoviridae family. Among filoviruses, Ebola virus (EBOV) and Marburg virus (MARV) are the most contagious viruses with mortality rates of 24%-90%. Phylogenetic analysis showed that MLAV was closely related to MARV among the members of filovirus family. MLAV enters into host cells via viral glycoprotein (GP). The recombinant virus study indicated that MLAV has a potential for bat-to-human cross-species transmission. In this study, a GP-mediated MLAV entry evaluating model was established, and by using this model, we investigated the susceptibility of MLAV to the human cell lines sourced from different tissues and the African green monkey kidney cell lines. Four compounds, chloroquine, tetrandrine, clomiphene, and toremifene, which were known as EBOV and MARV entry blockers, were tested for HIV/MLAV-GP infection. It was found that chloroquine effectively blocked the entry of MLAV with the half maximal effective concentration (EC50) of 1.56 μmol·L-1, resembling its anti-EBOV and -MARV activities. To the best of our acknowledge, there is no anti-MLAV drug reported by far, and the identification of chloroquine as an MLAV entry inhibitor may provide an insight for developing anti-filovirus agents.

Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

Ébola: Un riesgo para la población en un mundo globalizado / EBOLA: a risk for the population in a global world

La enfermedad por virus Ebola fue identificada por primera vez como una epidemia mortal en Nzara en el sur de Sudán y en Yambuku en el norte de la República Democrática del Congo (RDC, antes Zaire) en 1976. Desde entonces, las epidemias por Ebola han sido reportadas en otros países de África Central, en dos períodos distintos, con una brecha aproximada de quince años de silencio. Recientemente se han reportado brotes en Guinea, Liberia, Nigeria y Sierra Leona que están generando preocupación mundial debido a que su propagación por contacto directo con una amplia variedad de fluidos corporales de un individuo infectado como sangre o secreciones (saliva, sudor, vómitos) y con objetos (como agujas) contaminados con secreciones infectantes coloca en riesgo a familiares y amigos que atienden a personas enfermas y especialmente al personal en establecimientos de salud, debido a que generalmente no disponen de equipos de bioseguridad, ni de adecuadas medidas de limpieza y eliminación de instrumentos para protegerse, se desconoce cómo las personas se infectan con el virus Ebola, existen medidas de prevención primaria, pero no hay ninguna vacuna disponible. Debido a la alta letalidad y a la posible dispersión y aparición de casos en otros continentes, el objetivo de la presente revisión está dirigido a describir las características clínico epidemiológicas de Ebola para actualizar el conocimiento de la enfermedad tanto en el personal de salud como en la población general y promover la toma de medidas de prevención para evitar su propagación.

Ebola virus disease was first identified in 1976 in Nzara southern Sudan, and in northern Yambuku in the Democratic Republic of Congo (DRC, formerly Zaire). Since then, Ebola epidemics have been reported in other countries in Central Africa, in two different periods, with an approximate gap of fifteen years of silence. Recent outbreaks have been reported in Guinea, Liberia, Nigeria and Sierra Leone, that are generating global concern due to its spread by direct contact with a wide variety of bodily fluids from an infected person as blood or secretions (saliva, sweat, vomit) and objects (such as needles) contaminated with infectious secretions, which pose a risk to family and friends caring for sick people and especially the staff in health facilities, because generally they lack equipment or adequate biosecurity measures for cleaning and disposing instruments for their protection. Currently, it is unknown how people become infected with the Ebola virus; there are measures for primary prevention, but there is no vaccine available. Due to the high case-fatality rates and possible spread and occurrence of cases in other continents, the aim of this review is aimed at describing the clinical and epidemiological characteristics of Ebola in order to update the knowledge about this disease in both health workers and the general population and promote the adoption of measures to prevent and avoid its spread.

Laboratory Detection and Diagnosis of Filoviruses / 中国病毒学·英文版

Ebola virus(EBOV)and Marburg virus(MARV),belonging to the Filoviridae family,emerged four decades ago and caused severe viral hemorrhagic fever in human and other primates.As high as 50-90% mortality,filoviruses can cause significant threats to public health.However,so far no specific and efficient vaccine has been available,nor have other treatment methods proved to be effective.It is of great importance to detect these pathogens specific,rapidly and sensitively in order to control future filovirus outbreaks.Here,recent progresses in the development of detection and diagnosis methods for EBOV and MARV are summarized.