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Even if Ebola has faded from the headlines, the danger remains. As the largest and most deadly outbreak of Ebola winds down, scientists and public health officials are looking closely at what it will take to finish the job and to prepare better for the next big crisis. The apparent success of a nimble and creative clinical trial for a vaccine is a positive and instructive outcome. But many of the most important lessons come from failures in preparedness.
Here you can follow Nature’s full coverage of the crisis, including the travails of reporter Erika Check Hayden who travelled to Sierra Leone in December 2014, along with recent research and archival coverage of Ebola’s past.
Wu-Chun Cao and colleagues report on how EBOV, the Ebola virus responsible for the ongoing epidemic in West Africa, has evolved. The authors describe 175 EBOV full-length genome sequences from five districts in Sierra Leone, collected between 28 September and 11 November 2014. They find a rate of virus evolution similar to that observed during previous EBOV outbreaks. The genetic diversity of the virus has increased substantially, with the emergence of several novel lineages. The sharp increase in genetic diversity underlines the importance of EBOV surveillance in Sierra Leone, Guinea and Liberia.
Wei-Feng Shi ⋯
The China Mobile Laboratory Testing Team in Sierra Leone
Etienne Simon-Loriere and colleagues provide new information about the evolution of the Ebola virus responsible for the epidemic in West Africa. They have obtained the sequences of 85 new Ebola virus genomes collected from patients infected from July to November 2014 in Guinea. They find evidence for sustained transmission of three co-circulating lineages, each defined by multiple mutations.
Miles Carroll and colleagues report describe the genetic evolution of Ebola virus circulating in West Africa, based on 179 new virus sequences from patient samples collected in Guinea between March 2014 and January 2015. Their analysis shows how different lineages evolved and spread in West Africa between Sierra Leone, Guinea and Liberia.
This study shows that ZMapp, an optimized cocktail of three monoclonal antibodies that has been pressed into clinical use in response to the current Ebola virus disease epidemic, was able to rescue all of 18 rhesus macaques when treatment was initiated up to five days post-infection. All three controls had died by day eight.
Viruses of the Filoviridae family can cause severe haemorrhagic fever in humans and non-human primates. Mortality rates are extremely high and no vaccines or drugs are currently licensed for the treatment of filovirus diseases. Here Sina Bavari and colleagues report the discovery of a small-molecule viral polymerase inhibitor with in vitro and in vivo antiviral activity against highly pathogenic viruses, including filoviruses such as Ebola virus and Sudan virus. The compound, BCX4430, is an adenosine analogue that acts as a non-obligate chain terminator. Administered either orally or intramuscularly, it can completely protect cynomolgus macaques from Marburg virus, even when administered as late as 48 hours after infection.
The search for therapeutics to treat infections by ebolaviruses and Marburg virus has focused on identifying compounds that interfere with viral entry into host cells. Here, White and Schornberg discuss recent studies that have identified Niemann–Pick C1 (NPC1), a protein that resides deep in the endocytic pathway, as an important host factor in this process.
The extraordinary virulence of the Ebola and Marburg filoviruses has spurred intensive research into the molecular mechanisms by which they multiply and cause disease. Carette et al. use a genome-wide genetic screen in human cells to identify factors required for entry of Ebola virus. The screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann–Pick C1 (NPC1). Côté et al. report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection in cell culture, with NPC1 being the target. The unexpected role for the hereditary disease gene NPC1 in Ebola virus infection may facilitate the development of antifilovirus therapeutics.