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. 2018;46(2):126-133.
doi: 10.1159/000487224. Epub 2018 Apr 26.

Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination

Benjamin Koch  1 , Patricia Schult-Dietrich  2 , Stefan Büttner  1 , Bijan Dilmaghani  1 , Dario Lohmann  1 , Patrick C Baer  1 , Ursula Dietrich  2 , Helmut Geiger  1
Affiliations

Lectin Affinity Plasmapheresis for Middle East Respiratory Syndrome-Coronavirus and Marburg Virus Glycoprotein Elimination

Benjamin Koch et al. Blood Purif. 2018.

Abstract

Background/aims: Middle East respiratory syndrome coronavirus (MERS-CoV) and Marburg virus (MARV) are among the World Health Organization's top 8 emerging pathogens. Both zoonoses share nonspecific early symptoms, a high lethality rate, and a reduced number of specific treatment options. Therefore, we evaluated extracorporeal virus and glycoprotein (GP) elimination by lectin affinity plasmapheresis (LAP).

Methods: For both MERS-CoV (pseudovirus) as well as MARV (GPs), 4 LAP devices (Mini Hemopurifiers, Aethlon Medical, San Diego, CA, USA) and 4 negative controls were tested. Samples were collected every 30 min and analyzed for reduction in virus infectivity by a flow cytometry-based infectivity assay (MERS-CoV) and in soluble GP content (MARV) by an immunoassay.

Results: The experiments show a time-dependent clearance of MERS-CoV of up to 80% within 3 h (pseudovirus). Up to 70% of MARV-soluble GPs were eliminated at the same time. Substantial saturation of the binding resins was detected within the first treatment hour.

Conclusion: MERS-CoV (pseudovirus) and MARV soluble GPs are eliminated by LAP in vitro. Considering the high lethality and missing established treatment options, LAP should be evaluated in vivo. Especially early initiation, continuous therapy, and timed cartridge exchanges could be of importance.

Keywords: Extracorporeal purification; Lectin affinity plasmapheresis; Marburg virus; Middle East respiratory syndrome coronavirus.

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Figures

Fig. 1.
Fig. 1.
LAP device. Galanthus nivalis (common snowdrop) lectin is placed in the extracapillary space of a standard plasma filter with 200 nm pore size. Enveloped viruses are affinity-captured by lectins. The purified plasma returns to the patient. LAP, lectin affinity plasmapheresis; MERS-CoV, middle east respiratory syndrome coronavirus; GNA, galanthus nivalis agglutinin; MARV GP, marburg virus glycoprotein.
Fig. 2.
Fig. 2.
MERS-CoV decrease in infectivity vs. time during LAP. The lower graph denotes the mean of 3 MERS-CoV pseudovirus experiments in complete medium. The upper graph shows a MERS-CoV pseudovirus serum experiment. Measurements were done by a flow cytometric infectivity assay. Controls (n = 4) were done with LAP devices without GNA. LAP, lectin affinity plasmapheresis; MERS-CoV, middle east respiratory syndrome coronavirus; GNA, galanthus nivalis agglutinin
Fig. 3.
Fig. 3.
Representative flow cytometric dot plot: MERS-CoV pseudovirus infections in HUH7 cells. LAP 0 vs. 180 min. There was a marked reduction of infected cells after LAP treatment (GFP positive cells). Measurement was by a cytometry-based infectivity assay using MERS-CoV pseudovirus expressing GFP. LAP, lectin affinity plasmapheresis; MERS-CoV, middle east respiratory syndrome coronavirus; GFP, green fluorescent protein.
Fig. 4.
Fig. 4.
MARV-GP clearance by LAP: concentration vs. time (measurements by immunoassay). The lower graph denotes the mean of 3 MARV GP experiments in complete medium, the upper one shows a MARV GP serum experiment. The controls were done with LAP devices without GNA. LAP, lectin affinity plasmapheresis; MERS-CoV, middle east respiratory syndrome coronavirus; GNA, galanthus nivalis agglutinin; MARV GP, marburg virus glycoprotein.
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