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.

An update on the 2014 Ebola outbreak in Western Africa

The recent Ebola outbreak in Western Africa was the most devastating outbreak witnessed in recent times. There have been remarkable local and international efforts to control the crisis. Ebola Virus Disease is the focus of immense research activity. The progression of events in the region has been evolving swiftly and it is of paramount importance to the medical community to be acquainted with the situation. Over 28 000 people were inflicted with the condition, over 11 000 have died. Novel data has emerged regarding modes of transmission, providing rationale for recent flare-ups. Similarly, studies on survivors are elucidating the later stages of the disease recovery process. Novel techniques for diagnosis are also discussed. Finally, the current research regarding treatment and vaccine development is reviewed, particularly the implementation of rVSV-ZEBOV vaccination programs.

An update on the 2014 Ebola outbreak in Western Africa

The recent Ebola outbreak in Western Africa was the most devastating outbreak witnessed in recent times. There have been remarkable local and international efforts to control the crisis. Ebola Virus Disease is the focus of immense research activity. The progression of events in the region has been evolving swiftly and it is of paramount importance to the medical community to be acquainted with the situation. Over 28000 people were inflicted with the condition, over 11000 have died. Novel data has emerged regarding modes of transmission, providing rationale for recent flare-ups. Similarly, studies on survivors are elucidating the later stages of the disease recovery process. Novel techniques for diagnosis are also discussed. Finally, the current research regarding treatment and vaccine development is reviewed, particularly the implementation of rVSV-ZEBOV vaccination programs.

Development of quality control methods of recombinant anti-EBOV antibodies / 中国药学杂志

OBJECTIVE: To establish quality control methods for recombinant anti-EBOV mAbs which are comprised by three anti-EBOV glycoprotein mAbs. METHODS: The binding-activity of recombinant humanized anti-EBOV mAbs to EBOV glycoprotein was evaluated by ELISA. Peptide map by LC-MS was used in the identification tests. Purity was analyzed by CE-SDS and SEC-HPLC. iCIEF was performed to measure the PI value and the charge heterogeneity. 2AB was labeled on the released glycan, and was analyzed by NP-HPLC and mass spectrometry. The concentration of polysorbate 20 was tested by HPLC. RESULTS: The EC50s of recombinant anti-EBOV mAbs were (12.53±1.62), (11.10±0.62) and (6.09±0.35) ng·mL-1, respectively. The theoretical sequence coverage rates of three mAbs were all above 95%. The main peak area percentages shown by non-reduced CE-SDS were (94.41±0.05)%, (95.58±0.17)% and (96.11±0.05)%. The peak area percentages of both heavy and light chain shown by reduced CE-SDS were (98.19±0.06)%, (97.97±0.03)% and (98.57±0.03)%. The main peak area percentages shown by SE-HPLC were (99.59±0.01)%, (99.56±0.01)% and (99.74±0.01)%. The isoelectric points of the main peak shown by iCIEF were (8.70±0.01),(8.26±0.01) and (8.85±0.01). The concentrations of polysorbate 20 were (0.34±0.00),(0.35±0.00) and (0.35±0.01) μg·mL-1, respectively. The glycan mapping analysis was relatively sensitive, and the percentage of fucosylated N linked glycan was less than 0.5%. CONCLUSION: Up-to-date quality control methods for recombinant anti-EBOV mAbs are established in this study, which may be used to ensure the safety, effectiveness and quality controllability of the product. The methods can provide technical assists to Ebola outbreak and be a reference of the quality control of other domestic cocktail monoclonal antibody products.

The 2013-2015 Ebola outbreak in West Africa

Zaire Ebola virus (EBOV) is a fatal human pathogen, with a high case fatality rate (CFR) averaging up to 78%. In March 2014, the World Health Organization (WHO) was made aware of a ZEBOV outbreak in rural Guinea, West Africa. Epidemiologic investigation linked the clinical and laboratory confirmed cases with the presumed first fatality of the outbreak in December 2013. EBOV from Guinea is a separate clade from other ZEBOV strains reported from the Democratic Republic of Congo (DRC) and Gabon. Since the outbreak in March, ZEBOV was also reported in Conakry, Guinea's capital and spread to other neighboring countries. In its largest outbreak, ZEBOV disease expanded through Guinea, Liberia, Sierra Leone, and Nigeria and to Spain, the USA, and the UK. The WHO declared the 2013-2015 West African Ebola epidemic a public health emergency of international concern considering its presumable capacity for further international spread. Early manifestations of EVD (Ebola virus disease) include a high fever, body aches, malaise, and fatigue. Severe diarrhea and other gastrointestinal manifestations such as vomiting were common, while bleeding was a more sporadic finding. The fatality rate was 43% and highest in patients aged > or = 45 years and the overall fitted mean incubation period was 10.3 days (95% CI 9.9~10.7). We present a review of the literature on the emergence of Ebola, and the epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed in Sierra Leone, Guinea, Liberia, Mali, the USA, and Spain, its zoonotic origin, and the transmission of ZEBOV, as well as presenting original literature on the current Ebola outbreak.

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.