Klinik für Neurochirurgie, Klinikum Lünen, St.-Marien-Hospital, Akad. Lehrkrankenhaus der Westfälische Wilhelms—Universität Münster, 44534 Lünen, Germany
Dimitrios Kanakis
Institute of Pathology, University of Nicosia Medical School, 2408 Egkomi, Cyprus
Mingdi Yan
Department of Chemistry, University of Massachusetts Lowell, 1 University Avenue, Lowell, MA 01854, USA
Jesús Jiménez-Barbero
CIC bioGUNE, Bizkaia Technology Park, Building 800, 48160 Derio, Spain
Tibor Kožár
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Šafárik University, Jesenná 5, 04001 Košice, Slovakia
Nikolay E. Nifantiev
Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia
Christian Vollmer
Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
Timo Brandenburger
Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
Detlef Kindgen-Milles
Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
Thomas Haak
Diabetes Klinik Bad Mergentheim, Theodor-Klotzbücher-Str. 12, 97980 Bad Mergentheim, Germany
Athanasios K. Petridis
Medical School, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure–function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood–brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.
