Antiviral activity of quercetin-3-β-O-D-glucoside against Zika virus infection

Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.

Virus inoculation and treatment regimens for evaluating anti-filovirus monoclonal antibody efficacy in vivo

The development of monoclonal antibodies to treat disease caused by filoviruses,particularly Ebola virus,has risen steeply in recent years thanks to several key studies demonstrating their remarkable therapeutic potential.The increased drive to develop new and better monoclonal antibodies has necessarily seen an increase in animal model efficacy testing,which is critical to the pre-clinical development of any novel countermeasure.Primary and secondary efficacy testing against filoviruses typically makes use of one or more rodent models(mice,guinea pigs,and occasionally hamsters)or the more recently described ferret model,although the exact choice of model depends on the specific filovirus being evaluated.Indeed,no single small animal model exists for all filoviruses,and the use of any given model must consider the nature of that model as well as the nature of the therapeutic and the experimental objectives.Confirmatory evaluation,on the other hand,is performed in nonhuman primates(rhesus or cynomolgus macaques)regardless of the filovirus.In light of the number of different animal models that are currently used in monoclonal antibody efficacy testing,we sought to better understand how these efficacy tests are being performed by numerous different laboratories around the world.To this end,we review the animal models that are being used for antibody efficacy testing against filoviruses,and we highlight the challenge doses and routes of infection that are used.We also describe the various antibody treatment regimens,including antibody dose,route,and schedule of administration,that are used in these model systems.We do not identify any single best model or treatment regimen,and we do not advocate for field-wide protocol standardization.Instead,we hope to provide a comprehensive resource that will facilitate and enhance the continued pre-clinical development of novel monoclonal antibody therapeutics.

Intra-host Ebola viral adaption during human infection

The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.

Can Ebola virus become endemic in the human population？

The 2014-15 Ebola virus reported during March 2014 Guinea. has shown itself to （EBOV） outbreak, originally n the Western African nation of be resistant to traditional con- tainment methods, with over 28,000 infections and 11,000 deaths over 18 months. Recently, news that a Scottish nurse had relapsed to EBOV disease with neurological symptoms at 10 months after recovery have astonished experts. The prolonged nature of the outbreak has led to questions whether EBOV can become endemic in the human popula- tion, an undesirable outcome due to the large amount of resources required to keep this virus under control. In this commentary, we discuss aspects EBOV disease with those caused by pathogens considered endemic in humans, as well as factors which may contribute to sustained EBOV transmission in humans.