TY - JOUR
T1 - Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms †
AU - Siebert, Hans Christian
AU - Eckert, Thomas
AU - Bhunia, Anirban
AU - Klatte, Nele
AU - Mohri, Marzieh
AU - Siebert, Simone
AU - Kozarova, Anna
AU - Hudson, John W.
AU - Zhang, Ruiyan
AU - Zhang, Ning
AU - Li, Lan
AU - Gousias, Konstantinos
AU - Kanakis, Dimitrios
AU - Yan, Mingdi
AU - Jiménez-Barbero, Jesús
AU - Kožár, Tibor
AU - Nifantiev, Nikolay E.
AU - Vollmer, Christian
AU - Brandenburger, Timo
AU - Kindgen-Milles, Detlef
AU - Haak, Thomas
AU - Petridis, Athanasios K.
N1 - Funding Information:
Access to the Utrecht University NMR Facility was funded by iNEXT-Discovery (grant 87103), an EC-funded project in the Framework Programme Horizon2020, project PID 13551 and the National Natural Science Foundation of China (No. 82001286), the Natural Science Foundation of Shandong province (No. ZR2020QH112) and the Open Project of Liaocheng University Animal Husbandry Discipline, No. 319312101-25. We are also grateful for financial support covering the publication fee from the non-profit organization Diabetes-Akademie Bad Mergentheim e. V. This publication also results from the project implementation: Open Scientific Community for Modern Interdisciplinary Research in Medicine (OPENMED), ITMS2014+: 313011V455 supported by the Operational Programme Integrated Infrastructure, funded by the ERDF.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - blood pH
KW - coronavirus fusion peptides
KW - incretin mimetics
KW - molecular modeling
KW - NMR
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85160767544&partnerID=8YFLogxK
U2 - 10.3390/biomedicines11051421
DO - 10.3390/biomedicines11051421
M3 - Article
AN - SCOPUS:85160767544
SN - 2227-9059
VL - 11
JO - Biomedicines
JF - Biomedicines
IS - 5
M1 - 1421
ER -