Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants

Lefebvre et al., Viruses, doi:10.3390/v16121836, Nov 2024
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
Lower risk for mortality, ventilation, ICU, hospitalization, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,300+ studies for 210+ treatments. c19early.org
Meta Analysis
In silico and in vitro study showing that ivermectin binds to the N-terminal domain (NTD) of the spike protein of SARS-CoV-2 variants, potentially inhibiting initial viral attachment to host cell lipid rafts. Authors used molecular modeling to identify an ivermectin binding site on the NTD that overlaps with the ganglioside binding domain. Ivermectin showed flexibility to adapt its binding to variants from the original Wuhan strain to Omicron subvariants. In vitro, ivermectin inhibited the binding of Wuhan and Alpha variant spike protein trimers to GM1 ganglioside monolayers.
74 preclinical studies support the efficacy of ivermectin for COVID-19:
34 in silico studies1-34
26 in vitro studies2,35-59
14 in vivo animal studies46,52,59-70
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N771, Dengue37,72,73, HIV-173, Simian virus 4074, Zika37,75,76, West Nile76, Yellow Fever77,78, Japanese encephalitis77, Chikungunya78, Semliki Forest virus78, Human papillomavirus57, Epstein-Barr57, BK Polyomavirus79, and Sindbis virus78.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins71,73,74,80, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing38, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination41,81, shows dose-dependent inhibition of wildtype and omicron variants36, exhibits dose-dependent inhibition of lung injury61,66, may inhibit SARS-CoV-2 via IMPase inhibition37, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation9, inhibits SARS-CoV-2 3CLpro54, may inhibit SARS-CoV-2 RdRp activity28, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages60, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation82, may interfere with SARS-CoV-2's immune evasion via ORF8 binding4, may inhibit SARS-CoV-2 by disrupting CD147 interaction83-86, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1959,87, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage8, may minimize SARS-CoV-2 induced cardiac damage40,48, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation88, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses1, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways35, increases Bifidobacteria which play a key role in the immune system89, has immunomodulatory51 and anti-inflammatory70,90 properties, and has an extensive and very positive safety profile91.
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Lefebvre et al., 27 Nov 2024, France, peer-reviewed, 4 authors. Contact: jacques.fantini@univ-amu.fr (corresponding author), marinelfv@gmail.com, bernard.la-scola@univ-amu.fr, henrichahinian@gmail.com.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants
Marine Lefebvre, Henri Chahinian, Bernard La Scola, Jacques Fantini
Viruses, doi:10.3390/v16121836
Most studies on the docking of ivermectin on the spike protein of SARS-CoV-2 concern the receptor binding domain (RBD) and, more precisely, the RBD interface recognized by the ACE2 receptor. The N-terminal domain (NTD), which controls the initial attachment of the virus to lipid raft gangliosides, has not received the attention it deserves. In this study, we combined molecular modeling and physicochemical approaches to analyze the mode of interaction of ivermectin with the interface of the NTD-facing lipid rafts of the host cell membrane. We characterize a binding area that presents point mutations and deletions in successive SARS-CoV-2 variants from the initial strain to omicron KP.3 circulating in many countries in 2024. We show that ivermectin has exceptional flexibility, allowing the drug to bind to the spike protein of all variants tested. The energy of interaction is specific to each variant, allowing a classification according to their affinity for ivermectin in the following ascending order: Omicron KP.3 < Delta < Omicron BA.5 < Alpha < Wuhan (B.1) < Omicron BA.1. The binding site of ivermectin is subject to important variations of the NTD, including the Y144 deletion. It overlaps with the ganglioside binding domain of the NTD, as demonstrated by docking and physicochemical studies. These results suggest a new mechanism of antiviral action for ivermectin based on competitive inhibition for initial virus attachment to lipid rafts. The current KP.3 variant is still recognized by ivermectin, although with an affinity slightly lower than the Wuhan strain.
Conflicts of Interest: The authors declare no conflicts of interest. Viruses 2024, 16, 1836
References
Allen, Introduction to molecular dynamics simulation, Comput. Soft Matter Synth. Polym. Proteins
Alonso, Bliznyuk, Gready, Combining docking and molecular dynamic simulations in drug design, Med. Res. Rev, doi:10.1002/med.20067
Amanat, Thapa, Lei, Ahmed, Adelsberg et al., SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2, Cell, doi:10.1016/j.cell.2021.06.005
Aminpour, Cannariato, Preto, Safaeeardebili, Moracchiato et al., In silico analysis of the multi-targeted mode of action of ivermectin and related compounds, Computation, doi:10.3390/computation10040051
Andreani, Le Bideau, Duflot, Jardot, Rolland et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb. Pathog, doi:10.1016/j.micpath.2020.104228
Andrei, Conjugate Gradient Methods
Ayodele, Bamigbade, Bamigbade, Adeniyi, Tachin et al., Illustrated Procedure to Perform Molecular Docking Using PyRx and Biovia Discovery Studio Visualizer: A Case Study of 10kt With Atropine, Prog. Drug Discov. Biomed. Sci, doi:10.36877/pddbs.a0000424
Borcik, Eason, Yekefallah, Amani, Han et al., A cholesterol dimer stabilizes the inactivated state of an inward-rectifier Potassium Channel, Angew. Chem. Int. Ed, doi:10.1002/anie.202112232
Borges-Araújo, Patmanidis, Singh, Santos, Sieradzan et al., Pragmatic coarse-graining of proteins: Models and applications, J. Chem. Theory Comput, doi:10.1021/acs.jctc.3c00733
Boschi, Scheim, Bancod, Militello, Bideau et al., SARS-CoV-2 spike protein induces hemagglutination: Implications for COVID-19 morbidities and therapeutics and for vaccine adverse effects, Int. J. Mol. Sci, doi:10.3390/ijms232415480
Branda, Ciccozzi, Scarpa, Features of the SARS-CoV-2 KP. 3 variant mutations, Infect. Dis, doi:10.1080/23744235.2024.2385500
Buttenschoen, Morris, Deane, Posebusters, AI-based docking methods fail to generate physically valid poses or generalise to novel sequences, Chem. Sci, doi:10.1039/D3SC04185A
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res, doi:10.1016/j.antiviral.2020.104787
Changeux, Edelstein, Conformational selection or induced fit? 50 years of debate resolved, Biol. Rep, doi:10.3410/B3-19
Chen, Beware of docking! Trends, Pharmacol. Sci, doi:10.1016/j.tips.2014.12.001
Choudhury, Das, Patra, Bhattacharya, Ghosh et al., Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: An in silico approach, Future Virol, doi:10.2217/fvl-2020-0342
Di Scala, Fantini, Hybrid In Silico/In Vitro Approaches for the Identification of Functional Cholesterol-Binding Domains in Membrane Proteins, Methods Mol. Biol, doi:10.1007/978-1-4939-6875-6_2
Di Scala, Troadec, Lelièvre, Garmy, Fantini et al., Mechanism of cholesterol-assisted oligomeric channel formation by a short Alzheimer β-amyloid peptide, J. Neurochem, doi:10.1111/jnc.12390
Dima, Salvagno, Lippi, Effects of recombinant SARS-CoV-2 spike protein variants on red blood cells parameters and red blood cell distribution width, Biomed. J, doi:10.1016/j.bj.2024.100787
Diociaiuti, Giordani, Kamel, Brasili, Sennato et al., Monosialoganglioside-GM1 triggers binding of the amyloid-protein salmon calcitonin to a Langmuir membrane model mimicking the occurrence of lipid-rafts, Biochem. Biophys. Rep, doi:10.1016/j.bbrep.2016.10.005
Elderdfi, Sikorski, Langmuir-monolayer methodologies for characterizing protein-lipid interactions, Chem. Phys. Lipids, doi:10.1016/j.chemphyslip.2018.01.008
Ewing, Makino, Skillman, Kuntz, Dock, 4.0: Search strategies for automated molecular docking of flexible molecule databases, J. Comput.-Aided Mol. Des, doi:10.1023/A:1011115820450
Fantini, Azzaz, Chahinian, Yahi, Electrostatic Surface Potential as a Key Parameter in Virus Transmission and Evolution: How to Manage Future Virus Pandemics in the Post-COVID-19 Era, Viruses, doi:10.3390/v15020284
Fantini, Chahinian, Yahi, Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future, Int. J. Mol. Sci, doi:10.3390/ijms24031923
Fantini, Chahinian, Yahi, Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2020.10.015
Fantini, Chahinian, Yahi, Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal, Int. J. Antimicrob. Agents, doi:10.1016/j.ijantimicag.2020.106020
Fantini, Di Scala, Chahinian, Yahi, Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection, Int. J. Antimicrob. Agents, doi:10.1016/j.ijantimicag.2020.105960
Fantini, Fundamental Mechanisms in Membrane Receptology: Old Paradigms, New Concepts and Perspectives, Receptors, doi:10.3390/receptors3010006
Fantini, Lipid rafts and human diseases: Why we need to target gangliosides, FEBS Open Bio, doi:10.1002/2211-5463.13612
Fantini, Yahi, Azzaz, Chahinian, Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks, J. Infect, doi:10.1016/j.jinf.2021.06.001
Fantini, Yahi, Colson, Chahinian, La Scola et al., The puzzling mutational landscape of the SARS-2-variant Omicron, J. Med. Virol, doi:10.1002/jmv.27577
Gaetano, Capasso, Delre, Pirone, Saviano et al., More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells, Int. J. Mol. Sci, doi:10.3390/ijms22126462
Ghoula, Naceri, Sitruk, Flatters, Moroy et al., Identifying promising druggable binding sites and their flexibility to target the receptor-binding domain of SARS-CoV-2 spike protein, Comput. Struct. Biotechnol. J, doi:10.1016/j.csbj.2023.03.029
Gianni, Dogan, Jemth, Distinguishing induced fit from conformational selection, Biophys. Chem, doi:10.1016/j.bpc.2014.03.003
Grippo, Lucidi, A globally convergent version of the Polak-Ribiere conjugate gradient method, Math. Program, doi:10.1007/BF02614362
Guex, Peitsch, SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling, Electrophoresis, doi:10.1002/elps.1150181505
Gyselinck, Janssens, Verhamme, Vos, Rationale for azithromycin in COVID-19: An overview of existing evidence, BMJ Open Respir. Res, doi:10.1136/bmjresp-2020-000806
Huang, Kalyanaraman, Bernacki, Jacobson, Molecular mechanics methods for predicting protein-ligand binding, Phys. Chem. Chem. Phys. PCCP, doi:10.1039/B608269F
Huang, Wong, Wheeler, Flexible protein-flexible ligand docking with disrupted velocity simulated annealing, Proteins, doi:10.1002/prot.21781
Islas, Scior, Allosteric Binding of MDMA to the Human Serotonin Transporter (hSERT) via Ensemble Binding Space Analysis with ∆G Calculations, Induced Fit Docking and Monte Carlo Simulations, Molecules, doi:10.3390/molecules27092977
Jaafar, Boschi, Aherfi, Bancod, Le Bideau et al., High individual heterogeneity of neutralizing activities against the original strain and nine different variants of SARS-CoV-2, Viruses, doi:10.3390/v13112177
Kaku, Uriu, Kosugi, Okumura, Yamasoba et al., Virological characteristics of the SARS-CoV-2 KP. 2 variant, Lancet Infect. Dis, doi:10.1016/S1473-3099(24)00298-6
Kaku, Yo, Tolentino, Uriu, Okumura et al., Virological characteristics of the SARS-CoV-2 KP. 3, LB. 1, and KP. 2.3 variants, Lancet Infect. Dis, doi:10.1016/S1473-3099(24)00415-8
Kharche, Sengupta, Dynamic protein interfaces and conformational landscapes of membrane protein complexes, Curr. Opin. Struct. Biol, doi:10.1016/j.sbi.2020.01.001
Khoda, Liu, Storey, Generalized Polak-Ribiere algorithm, J. Optim. Theory Appl, doi:10.1007/BF00941472
Kim, Cha, Choi, Kim, Omega class glutathione S-transferase: Antioxidant enzyme in pathogenesis of neurodegenerative diseases, Oxidative Med. Cell. Longev, doi:10.1155/2017/5049532
Kim, Chivian, Baker, Protein structure prediction and analysis using the Robetta server, Nucleic Acids Res, doi:10.1093/nar/gkh468
Klatzmann, Mcdougal, Maddon, The CD4 molecule and HIV infection, Immunodefic. Rev
Lan, Ge, Yu, Shan, Zhou et al., Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, Nature, doi:10.1038/s41586-020-2180-5
Liu, Bakker, Narimatsu, Van Kuppeveld, Clausen et al., H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2304992120
Low, Yip, Lal, Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication, Biochim. Biophys. Acta-Mol. Basis Dis, doi:10.1016/j.bbadis.2021.166294
Maginnis, Virus-Receptor Interactions: The Key to Cellular Invasion, J. Mol. Biol, doi:10.1016/j.jmb.2018.06.024
Maresca, Derghal, Caravagna, Dudin, Fantini, Controlled aggregation of adenine by sugars: Physicochemical studies, molecular modelling simulations of sugar-aromatic CH-pi stacking interactions, and biological significance, Phys. Chem. Chem. Phys. PCCP, doi:10.1039/b802594k
Matveeva, Lefebvre, Chahinian, Yahi, Fantini, Host membranes as drivers of virus evolution, Viruses, doi:10.3390/v15091854
Mcdougal, Maddon, Dalgleish, Clapham, Littman et al., The T4 glycoprotein is a cell-surface receptor for the AIDS virus, Cold Spring Harb. Symp. Quant. Biol, doi:10.1101/SQB.1986.051.01.083
Milanetti, Miotto, Di Rienzo, Nagaraj, Monti et al., In-silico evidence for a two receptor based strategy of SARS-CoV-2, Front. Mol. Biosci, doi:10.3389/fmolb.2021.690655
Monti, Milanetti, Frans, Miotto, Di Rienzo et al., Two Receptor Binding Strategy of SARS-CoV-2 Is Mediated by Both the N-Terminal and Receptor-Binding Spike Domain, J. Phys. Chem. B, doi:10.1021/acs.jpcb.3c06258
Nocedal, Wright, Conjugate gradient methods
Paggi, Pandit, Dror, The Art and Science of Molecular Docking, Annu. Rev. Biochem, doi:10.1146/annurev-biochem-030222-120000
Sarkar, Concilio, Sessa, Marrafino, Piotto, Advancements and novel approaches in modified autodock vina algorithms for enhanced molecular docking, Results Chem, doi:10.1016/j.rechem.2024.101319
Scheim, A deadly embrace: Hemagglutination mediated by SARS-CoV-2 spike protein at its 22 N-glycosylation sites, red blood cell surface sialoglycoproteins, and antibody, Int. J. Mol. Sci, doi:10.3390/ijms23052558
Scheim, Vottero, Santin, Hirsh, Sialylated glycan bindings from SARS-CoV-2 spike protein to blood and endothelial cells govern the severe morbidities of COVID-19, Int. J. Mol. Sci, doi:10.3390/ijms242317039
Seyran, Takayama, Uversky, Lundstrom, Palù et al., The structural basis of accelerated host cell entry by SARS-CoV-2, FEBS J, doi:10.1111/febs.15651
Shang, Ye, Shi, Wan, Luo et al., Structural basis of receptor recognition by SARS-CoV-2, Nature, doi:10.1038/s41586-020-2179-y
Shanmugaraj, Ever-evolving SARS-CoV-2: Latest variant KP. 2 is on the rise, Asian Pac. J. Trop. Med, doi:10.4103/apjtm.apjtm_341_24
Sinha, Tam, Wang, Applications of molecular dynamics simulation in protein study, Membranes, doi:10.3390/membranes12090844
Sokkar, Mohandass, Ramachandran, Multiple templates-based homology modeling enhances structure quality of AT1 receptor: Validation by molecular dynamics and antagonist docking, J. Mol. Model, doi:10.1007/s00894-010-0860-z
Srinivasu, Babu, Rao, Energy Minimization of CDK2 bound ligands: A Computational Approach, Int. J. Eng. Res. Appl
Ströh, Nagarathinam, Krey, Conformational flexibility in the CD81-binding site of the hepatitis C virus glycoprotein E2, Front. Immunol, doi:10.3389/fimmu.2018.01396
Sun, The role of cell surface sialic acids for SARS-CoV-2 infection, Glycobiology, doi:10.1093/glycob/cwab032
Suryadevara, Shrihari, Gilchuk, Vanblargan, Binshtein et al., Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein, Cell, doi:10.1016/j.cell.2021.03.029
Thakur, Micic, Leblanc, Surface chemistry of Alzheimer's disease: A Langmuir monolayer approach, Colloids Surf. B Biointerfaces, doi:10.1016/j.colsurfb.2009.07.043
Thomsen, Christensen, Moldock, A new technique for high-accuracy molecular docking, J. Med. Chem, doi:10.1021/jm051197e
Tronrud, Introduction to macromolecular refinement, Acta Crystallogr. Sect. D Biol. Crystallogr, doi:10.1107/S090744490402356X
Trott, Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem, doi:10.1002/jcc.21334
Tsuji, Docking Study with HyperChem, Revision G1
Tsuji, Homology Modeling Professional for HyperChem
Tsuji, Shudo, Kagechika, Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors, J. Comput.-Aided Mol. Des, doi:10.1007/s10822-015-9869-9
Uversky, Intrinsically disordered proteins and novel strategies for drug discovery, Expert Opin. Drug Discov, doi:10.1517/17460441.2012.686489
Uversky, Intrinsically disordered proteins and their environment: Effects of strong denaturants, temperature, pH, counter ions, membranes, binding partners, osmolytes, and macromolecular crowding, Protein J, doi:10.1007/s10930-009-9201-4
Uversky, Introduction to intrinsically disordered proteins (IDPs), Chem. Rev, doi:10.1021/cr500288y
Wlodarski, Zagrovic, Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin, Proc. Natl. Acad. Sci, doi:10.1073/pnas.0906966106
Zaidi, Dehgani-Mobaraki, The mechanisms of action of ivermectin against SARS-CoV-2-An extensive review, J. Antibiot, doi:10.1038/s41429-021-00491-6
Zhao, Caflisch, Molecular dynamics in drug design, Eur. J. Med. Chem, doi:10.1016/j.ejmech.2014.08.004
DOI record: { "DOI": "10.3390/v16121836", "ISSN": [ "1999-4915" ], "URL": "http://dx.doi.org/10.3390/v16121836", "abstract": "<jats:p>Most studies on the docking of ivermectin on the spike protein of SARS-CoV-2 concern the receptor binding domain (RBD) and, more precisely, the RBD interface recognized by the ACE2 receptor. The N-terminal domain (NTD), which controls the initial attachment of the virus to lipid raft gangliosides, has not received the attention it deserves. In this study, we combined molecular modeling and physicochemical approaches to analyze the mode of interaction of ivermectin with the interface of the NTD-facing lipid rafts of the host cell membrane. We characterize a binding area that presents point mutations and deletions in successive SARS-CoV-2 variants from the initial strain to omicron KP.3 circulating in many countries in 2024. We show that ivermectin has exceptional flexibility, allowing the drug to bind to the spike protein of all variants tested. The energy of interaction is specific to each variant, allowing a classification according to their affinity for ivermectin in the following ascending order: Omicron KP.3 &lt; Delta &lt; Omicron BA.5 &lt; Alpha &lt; Wuhan (B.1) &lt; Omicron BA.1. The binding site of ivermectin is subject to important variations of the NTD, including the Y144 deletion. It overlaps with the ganglioside binding domain of the NTD, as demonstrated by docking and physicochemical studies. These results suggest a new mechanism of antiviral action for ivermectin based on competitive inhibition for initial virus attachment to lipid rafts. 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Symp. Quant. Biol.", "key": "ref_1", "volume": "51", "year": "1986" }, { "article-title": "The CD4 molecule and HIV infection", "author": "Klatzmann", "first-page": "43", "journal-title": "Immunodefic. Rev.", "key": "ref_2", "volume": "2", "year": "1990" }, { "DOI": "10.1038/s41586-020-2179-y", "article-title": "Structural basis of receptor recognition by SARS-CoV-2", "author": "Shang", "doi-asserted-by": "crossref", "first-page": "221", "journal-title": "Nature", "key": "ref_3", "volume": "581", "year": "2020" }, { "DOI": "10.1016/j.jmb.2018.06.024", "article-title": "Virus–Receptor Interactions: The Key to Cellular Invasion", "author": "Maginnis", "doi-asserted-by": "crossref", "first-page": "2590", "journal-title": "J. Mol. Biol.", "key": "ref_4", "volume": "430", "year": "2018" }, { "DOI": "10.3390/v15020284", "doi-asserted-by": "crossref", "key": "ref_5", "unstructured": "Fantini, J., Azzaz, F., Chahinian, H., and Yahi, N. (2023). Electrostatic Surface Potential as a Key Parameter in Virus Transmission and Evolution: How to Manage Future Virus Pandemics in the Post-COVID-19 Era. Viruses, 15." }, { "DOI": "10.3390/v15091854", "doi-asserted-by": "crossref", "key": "ref_6", "unstructured": "Matveeva, M., Lefebvre, M., Chahinian, H., Yahi, N., and Fantini, J. (2023). Host membranes as drivers of virus evolution. Viruses, 15." }, { "DOI": "10.3390/ijms24031923", "doi-asserted-by": "crossref", "key": "ref_7", "unstructured": "Fantini, J., Chahinian, H., and Yahi, N. (2023). Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future. Int. J. Mol. Sci., 24." }, { "DOI": "10.3389/fmolb.2021.690655", "doi-asserted-by": "crossref", "key": "ref_8", "unstructured": "Milanetti, E., Miotto, M., Di Rienzo, L., Nagaraj, M., Monti, M., Golbek, T.W., Gosti, G., Roeters, S.J., Weidner, T., and Otzen, D.E. (2021). In-silico evidence for a two receptor based strategy of SARS-CoV-2. Front. Mol. Biosci., 8." }, { "DOI": "10.1021/acs.jpcb.3c06258", "article-title": "Two Receptor Binding Strategy of SARS-CoV-2 Is Mediated by Both the N-Terminal and Receptor-Binding Spike Domain", "author": "Monti", "doi-asserted-by": "crossref", "first-page": "451", "journal-title": "J. Phys. Chem. B", "key": "ref_9", "volume": "128", "year": "2024" }, { "DOI": "10.1016/j.ijantimicag.2020.105960", "article-title": "Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "105960", "journal-title": "Int. J. Antimicrob. Agents", "key": "ref_10", "volume": "55", "year": "2020" }, { "DOI": "10.1016/j.bbrc.2020.10.015", "article-title": "Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "132", "journal-title": "Biochem. Biophys. Res. Commun.", "key": "ref_11", "volume": "538", "year": "2021" }, { "DOI": "10.1111/febs.15651", "article-title": "The structural basis of accelerated host cell entry by SARS-CoV-2", "author": "Seyran", "doi-asserted-by": "crossref", "first-page": "5010", "journal-title": "FEBS J.", "key": "ref_12", "volume": "288", "year": "2021" }, { "DOI": "10.1038/s41586-020-2180-5", "article-title": "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor", "author": "Lan", "doi-asserted-by": "crossref", "first-page": "215", "journal-title": "Nature", "key": "ref_13", "volume": "581", "year": "2020" }, { "DOI": "10.1016/j.cell.2021.03.029", "article-title": "Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein", "author": "Suryadevara", "doi-asserted-by": "crossref", "first-page": "2316", "journal-title": "Cell", "key": "ref_14", "volume": "184", "year": "2021" }, { "DOI": "10.1016/j.cell.2021.06.005", "article-title": "SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2", "author": "Amanat", "doi-asserted-by": "crossref", "first-page": "3936", "journal-title": "Cell", "key": "ref_15", "volume": "184", "year": "2021" }, { "DOI": "10.3390/v13112177", "doi-asserted-by": "crossref", "key": "ref_16", "unstructured": "Jaafar, R., Boschi, C., Aherfi, S., Bancod, A., Le Bideau, M., Edouard, S., Colson, P., Chahinian, H., Raoult, D., and Yahi, N. (2021). High individual heterogeneity of neutralizing activities against the original strain and nine different variants of SARS-CoV-2. Viruses, 13." }, { "DOI": "10.1016/j.ijantimicag.2020.106020", "article-title": "Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "106020", "journal-title": "Int. J. Antimicrob. Agents", "key": "ref_17", "volume": "56", "year": "2020" }, { "DOI": "10.1136/bmjresp-2020-000806", "article-title": "Rationale for azithromycin in COVID-19: An overview of existing evidence", "author": "Gyselinck", "doi-asserted-by": "crossref", "first-page": "e000806", "journal-title": "BMJ Open Respir. Res.", "key": "ref_18", "volume": "8", "year": "2021" }, { "DOI": "10.1016/j.micpath.2020.104228", "article-title": "In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect", "author": "Andreani", "doi-asserted-by": "crossref", "first-page": "104228", "journal-title": "Microb. Pathog.", "key": "ref_19", "volume": "145", "year": "2020" }, { "DOI": "10.1016/j.antiviral.2020.104787", "article-title": "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro", "author": "Caly", "doi-asserted-by": "crossref", "first-page": "104787", "journal-title": "Antivir. Res.", "key": "ref_20", "volume": "178", "year": "2020" }, { "DOI": "10.1016/j.bbadis.2021.166294", "doi-asserted-by": "crossref", "key": "ref_21", "unstructured": "Low, Z.Y., Yip, A.J.W., and Lal, S.K. (2022). Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication. Biochim. Biophys. Acta-Mol. Basis Dis., 1868." }, { "DOI": "10.1080/23744235.2024.2385500", "article-title": "Features of the SARS-CoV-2 KP. 3 variant mutations", "author": "Branda", "doi-asserted-by": "crossref", "first-page": "894", "journal-title": "Infect. Dis.", "key": "ref_22", "volume": "56", "year": "2024" }, { "DOI": "10.1016/S1473-3099(24)00298-6", "article-title": "Virological characteristics of the SARS-CoV-2 KP. 2 variant", "author": "Kaku", "doi-asserted-by": "crossref", "first-page": "e416", "journal-title": "Lancet Infect. Dis.", "key": "ref_23", "volume": "24", "year": "2024" }, { "DOI": "10.1016/S1473-3099(24)00415-8", "article-title": "Virological characteristics of the SARS-CoV-2 KP. 3, LB. 1, and KP. 2.3 variants", "author": "Kaku", "doi-asserted-by": "crossref", "first-page": "e482", "journal-title": "Lancet Infect. Dis.", "key": "ref_24", "volume": "24", "year": "2024" }, { "DOI": "10.4103/apjtm.apjtm_341_24", "article-title": "Ever-evolving SARS-CoV-2: Latest variant KP. 2 is on the rise", "author": "Shanmugaraj", "doi-asserted-by": "crossref", "first-page": "241", "journal-title": "Asian Pac. J. Trop. Med.", "key": "ref_25", "volume": "17", "year": "2024" }, { "DOI": "10.1016/j.jinf.2021.06.001", "article-title": "Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "197", "journal-title": "J. Infect.", "key": "ref_26", "volume": "83", "year": "2021" }, { "DOI": "10.1093/nar/gkh468", "article-title": "Protein structure prediction and analysis using the Robetta server", "author": "Kim", "doi-asserted-by": "crossref", "first-page": "W526", "journal-title": "Nucleic Acids Res.", "key": "ref_27", "volume": "32", "year": "2004" }, { "DOI": "10.1002/elps.1150181505", "article-title": "SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling", "author": "Guex", "doi-asserted-by": "crossref", "first-page": "2714", "journal-title": "Electrophoresis", "key": "ref_28", "volume": "18", "year": "1997" }, { "DOI": "10.1155/2017/5049532", "article-title": "Omega class glutathione S-transferase: Antioxidant enzyme in pathogenesis of neurodegenerative diseases", "author": "Kim", "doi-asserted-by": "crossref", "first-page": "5049532", "journal-title": "Oxidative Med. Cell. Longev.", "key": "ref_29", "volume": "2017", "year": "2017" }, { "key": "ref_30", "unstructured": "Tsuji, M. (2015). Docking Study with HyperChem, Revision G1, Institute of Molecular Function." }, { "DOI": "10.1007/s10822-015-9869-9", "article-title": "Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors", "author": "Tsuji", "doi-asserted-by": "crossref", "first-page": "975", "journal-title": "J. Comput.-Aided Mol. Des.", "key": "ref_31", "volume": "29", "year": "2015" }, { "key": "ref_32", "unstructured": "Tsuji, M. (2015). Homology Modeling Professional for HyperChem, Revision G1, Institute of Molecular Function." }, { "article-title": "Energy Minimization of CDK2 bound ligands: A Computational Approach", "author": "Srinivasu", "first-page": "1884", "journal-title": "Int. J. Eng. Res. Appl.", "key": "ref_33", "volume": "2", "year": "2012" }, { "DOI": "10.1021/jm051197e", "article-title": "MolDock: A new technique for high-accuracy molecular docking", "author": "Thomsen", "doi-asserted-by": "crossref", "first-page": "3315", "journal-title": "J. Med. Chem.", "key": "ref_34", "volume": "49", "year": "2006" }, { "DOI": "10.1016/j.colsurfb.2009.07.043", "article-title": "Surface chemistry of Alzheimer’s disease: A Langmuir monolayer approach", "author": "Thakur", "doi-asserted-by": "crossref", "first-page": "436", "journal-title": "Colloids Surf. B Biointerfaces", "key": "ref_35", "volume": "74", "year": "2009" }, { "DOI": "10.1016/j.chemphyslip.2018.01.008", "article-title": "Langmuir-monolayer methodologies for characterizing protein-lipid interactions", "author": "Elderdfi", "doi-asserted-by": "crossref", "first-page": "61", "journal-title": "Chem. Phys. Lipids", "key": "ref_36", "volume": "212", "year": "2018" }, { "article-title": "Monosialoganglioside-GM1 triggers binding of the amyloid-protein salmon calcitonin to a Langmuir membrane model mimicking the occurrence of lipid-rafts", "author": "Diociaiuti", "first-page": "365", "journal-title": "Biochem. Biophys. Rep.", "key": "ref_37", "volume": "8", "year": "2016" }, { "DOI": "10.1007/978-1-4939-6875-6_2", "article-title": "Hybrid In Silico/In Vitro Approaches for the Identification of Functional Cholesterol-Binding Domains in Membrane Proteins", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "7", "journal-title": "Methods Mol. Biol.", "key": "ref_38", "volume": "1583", "year": "2017" }, { "DOI": "10.36877/pddbs.a0000424", "article-title": "Illustrated Procedure to Perform Molecular Docking Using PyRx and Biovia Discovery Studio Visualizer: A Case Study of 10kt With Atropine", "author": "Ayodele", "doi-asserted-by": "crossref", "first-page": "1", "journal-title": "Prog. Drug Discov. Biomed. Sci.", "key": "ref_39", "volume": "6", "year": "2023" }, { "DOI": "10.1023/A:1011115820450", "article-title": "DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases", "author": "Ewing", "doi-asserted-by": "crossref", "first-page": "411", "journal-title": "J. Comput.-Aided Mol. Des.", "key": "ref_40", "volume": "15", "year": "2001" }, { "DOI": "10.1002/jcc.21334", "article-title": "AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading", "author": "Trott", "doi-asserted-by": "crossref", "first-page": "455", "journal-title": "J. Comput. Chem.", "key": "ref_41", "volume": "31", "year": "2010" }, { "DOI": "10.1146/annurev-biochem-030222-120000", "article-title": "The Art and Science of Molecular Docking", "author": "Paggi", "doi-asserted-by": "crossref", "first-page": "389", "journal-title": "Annu. Rev. Biochem.", "key": "ref_42", "volume": "93", "year": "2024" }, { "DOI": "10.1016/j.tips.2014.12.001", "article-title": "Beware of docking!", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "78", "journal-title": "Trends Pharmacol. Sci.", "key": "ref_43", "volume": "36", "year": "2015" }, { "DOI": "10.1039/D3SC04185A", "article-title": "PoseBusters: AI-based docking methods fail to generate physically valid poses or generalise to novel sequences", "author": "Buttenschoen", "doi-asserted-by": "crossref", "first-page": "3130", "journal-title": "Chem. Sci.", "key": "ref_44", "volume": "15", "year": "2024" }, { "DOI": "10.1016/j.rechem.2024.101319", "article-title": "Advancements and novel approaches in modified autodock vina algorithms for enhanced molecular docking", "author": "Sarkar", "doi-asserted-by": "crossref", "first-page": "101319", "journal-title": "Results Chem.", "key": "ref_45", "volume": "7", "year": "2024" }, { "DOI": "10.1002/prot.21781", "article-title": "Flexible protein-flexible ligand docking with disrupted velocity simulated annealing", "author": "Huang", "doi-asserted-by": "crossref", "first-page": "440", "journal-title": "Proteins", "key": "ref_46", "volume": "71", "year": "2008" }, { "DOI": "10.3410/B3-19", "doi-asserted-by": "crossref", "key": "ref_47", "unstructured": "Changeux, J.-P., and Edelstein, S. (2011). Conformational selection or induced fit? 50 years of debate resolved. F1000 Biol. Rep., 3." }, { "DOI": "10.1016/j.bpc.2014.03.003", "article-title": "Distinguishing induced fit from conformational selection", "author": "Gianni", "doi-asserted-by": "crossref", "first-page": "33", "journal-title": "Biophys. Chem.", "key": "ref_48", "volume": "189", "year": "2014" }, { "DOI": "10.1073/pnas.0906966106", "article-title": "Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin", "author": "Wlodarski", "doi-asserted-by": "crossref", "first-page": "19346", "journal-title": "Proc. Natl. Acad. Sci. USA", "key": "ref_49", "volume": "106", "year": "2009" }, { "DOI": "10.3390/molecules27092977", "doi-asserted-by": "crossref", "key": "ref_50", "unstructured": "Islas, Á.A., and Scior, T. (2022). Allosteric Binding of MDMA to the Human Serotonin Transporter (hSERT) via Ensemble Binding Space Analysis with ΔG Calculations, Induced Fit Docking and Monte Carlo Simulations. Molecules, 27." }, { "DOI": "10.1007/s10930-009-9201-4", "article-title": "Intrinsically disordered proteins and their environment: Effects of strong denaturants, temperature, pH, counter ions, membranes, binding partners, osmolytes, and macromolecular crowding", "author": "Uversky", "doi-asserted-by": "crossref", "first-page": "305", "journal-title": "Protein J.", "key": "ref_51", "volume": "28", "year": "2009" }, { "DOI": "10.1517/17460441.2012.686489", "article-title": "Intrinsically disordered proteins and novel strategies for drug discovery", "author": "Uversky", "doi-asserted-by": "crossref", "first-page": "475", "journal-title": "Expert Opin. Drug Discov.", "key": "ref_52", "volume": "7", "year": "2012" }, { "DOI": "10.1021/cr500288y", "article-title": "Introduction to intrinsically disordered proteins (IDPs)", "author": "Uversky", "doi-asserted-by": "crossref", "first-page": "6557", "journal-title": "Chem. Rev.", "key": "ref_53", "volume": "114", "year": "2014" }, { "DOI": "10.1039/B608269F", "article-title": "Molecular mechanics methods for predicting protein-ligand binding", "author": "Huang", "doi-asserted-by": "crossref", "first-page": "5166", "journal-title": "Phys. Chem. Chem. Phys. PCCP", "key": "ref_54", "volume": "8", "year": "2006" }, { "article-title": "Introduction to molecular dynamics simulation", "author": "Allen", "first-page": "1", "journal-title": "Comput. Soft Matter Synth. Polym. Proteins", "key": "ref_55", "volume": "23", "year": "2004" }, { "DOI": "10.1007/s00894-010-0860-z", "article-title": "Multiple templates-based homology modeling enhances structure quality of AT1 receptor: Validation by molecular dynamics and antagonist docking", "author": "Sokkar", "doi-asserted-by": "crossref", "first-page": "1565", "journal-title": "J. Mol. Model.", "key": "ref_56", "volume": "17", "year": "2011" }, { "DOI": "10.1016/j.ejmech.2014.08.004", "article-title": "Molecular dynamics in drug design", "author": "Zhao", "doi-asserted-by": "crossref", "first-page": "4", "journal-title": "Eur. J. Med. Chem.", "key": "ref_57", "volume": "91", "year": "2015" }, { "DOI": "10.1002/med.20067", "article-title": "Combining docking and molecular dynamic simulations in drug design", "author": "Alonso", "doi-asserted-by": "crossref", "first-page": "531", "journal-title": "Med. Res. Rev.", "key": "ref_58", "volume": "26", "year": "2006" }, { "DOI": "10.1002/anie.202112232", "article-title": "A cholesterol dimer stabilizes the inactivated state of an inward-rectifier Potassium Channel", "author": "Borcik", "doi-asserted-by": "crossref", "first-page": "e202112232", "journal-title": "Angew. Chem. Int. Ed.", "key": "ref_59", "volume": "61", "year": "2022" }, { "DOI": "10.3390/membranes12090844", "doi-asserted-by": "crossref", "key": "ref_60", "unstructured": "Sinha, S., Tam, B., and Wang, S.M. (2022). Applications of molecular dynamics simulation in protein study. Membranes, 12." }, { "DOI": "10.1016/j.sbi.2020.01.001", "article-title": "Dynamic protein interfaces and conformational landscapes of membrane protein complexes", "author": "Kharche", "doi-asserted-by": "crossref", "first-page": "191", "journal-title": "Curr. Opin. Struct. Biol.", "key": "ref_61", "volume": "61", "year": "2020" }, { "DOI": "10.1021/acs.jctc.3c00733", "article-title": "Pragmatic coarse-graining of proteins: Models and applications", "author": "Patmanidis", "doi-asserted-by": "crossref", "first-page": "7112", "journal-title": "J. Chem. Theory Comput.", "key": "ref_62", "volume": "19", "year": "2023" }, { "DOI": "10.1007/978-0-387-40065-5_5", "doi-asserted-by": "crossref", "key": "ref_63", "unstructured": "Nocedal, J., and Wright, S.J. (2006). Conjugate gradient methods. Numerical Optimization, Springer." }, { "DOI": "10.1007/978-3-031-08720-2_5", "doi-asserted-by": "crossref", "key": "ref_64", "unstructured": "Andrei, N. (2022). Conjugate Gradient Methods. Modern Numerical Nonlinear Optimization, Springer International Publishing." }, { "DOI": "10.1007/BF02614362", "article-title": "A globally convergent version of the Polak-Ribiere conjugate gradient method", "author": "Grippo", "doi-asserted-by": "crossref", "first-page": "375", "journal-title": "Math. Program.", "key": "ref_65", "volume": "78", "year": "1997" }, { "DOI": "10.1007/BF00941472", "article-title": "Generalized Polak-Ribiere algorithm", "author": "Khoda", "doi-asserted-by": "crossref", "first-page": "345", "journal-title": "J. Optim. Theory Appl.", "key": "ref_66", "volume": "75", "year": "1992" }, { "DOI": "10.1039/b802594k", "article-title": "Controlled aggregation of adenine by sugars: Physicochemical studies, molecular modelling simulations of sugar-aromatic CH-pi stacking interactions, and biological significance", "author": "Maresca", "doi-asserted-by": "crossref", "first-page": "2792", "journal-title": "Phys. Chem. Chem. Phys. PCCP", "key": "ref_67", "volume": "10", "year": "2008" }, { "DOI": "10.1107/S090744490402356X", "article-title": "Introduction to macromolecular refinement", "author": "Tronrud", "doi-asserted-by": "crossref", "first-page": "2156", "journal-title": "Acta Crystallogr. Sect. D Biol. Crystallogr.", "key": "ref_68", "volume": "60", "year": "2004" }, { "DOI": "10.1111/jnc.12390", "article-title": "Mechanism of cholesterol-assisted oligomeric channel formation by a short Alzheimer β-amyloid peptide", "author": "Troadec", "doi-asserted-by": "crossref", "first-page": "186", "journal-title": "J. Neurochem.", "key": "ref_69", "volume": "128", "year": "2014" }, { "DOI": "10.2217/fvl-2020-0342", "article-title": "Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: An in silico approach", "author": "Choudhury", "doi-asserted-by": "crossref", "first-page": "277", "journal-title": "Future Virol.", "key": "ref_70", "volume": "16", "year": "2021" }, { "DOI": "10.3390/computation10040051", "doi-asserted-by": "crossref", "key": "ref_71", "unstructured": "Aminpour, M., Cannariato, M., Preto, J., Safaeeardebili, M.E., Moracchiato, A., Doria, D., Donato, F., Zizzi, E.A., Deriu, M.A., and Scheim, D.E. (2022). In silico analysis of the multi-targeted mode of action of ivermectin and related compounds. Computation, 10." }, { "DOI": "10.1093/glycob/cwab032", "article-title": "The role of cell surface sialic acids for SARS-CoV-2 infection", "author": "Sun", "doi-asserted-by": "crossref", "first-page": "1245", "journal-title": "Glycobiology", "key": "ref_72", "volume": "31", "year": "2021" }, { "DOI": "10.3390/ijms22126462", "doi-asserted-by": "crossref", "key": "ref_73", "unstructured": "Di Gaetano, S., Capasso, D., Delre, P., Pirone, L., Saviano, M., Pedone, E., and Mangiatordi, G.F. (2021). More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells. Int. J. Mol. Sci., 22." }, { "DOI": "10.1101/2022.11.24.517882", "doi-asserted-by": "crossref", "key": "ref_74", "unstructured": "Boschi, C., Scheim, D.E., Bancod, A., Militello, M., Bideau, M.L., Colson, P., Fantini, J., and Scola, B.L. (2022). SARS-CoV-2 spike protein induces hemagglutination: Implications for COVID-19 morbidities and therapeutics and for vaccine adverse effects. Int. J. Mol. Sci., 23." }, { "DOI": "10.1002/jmv.27577", "article-title": "The puzzling mutational landscape of the SARS-2-variant Omicron", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "2019", "journal-title": "J. Med. Virol.", "key": "ref_75", "volume": "94", "year": "2022" }, { "DOI": "10.1002/2211-5463.13612", "article-title": "Lipid rafts and human diseases: Why we need to target gangliosides", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "1636", "journal-title": "FEBS Open Bio", "key": "ref_76", "volume": "13", "year": "2023" }, { "DOI": "10.3390/receptors3010006", "article-title": "Fundamental Mechanisms in Membrane Receptology: Old Paradigms, New Concepts and Perspectives", "author": "Fantini", "doi-asserted-by": "crossref", "first-page": "107", "journal-title": "Receptors", "key": "ref_77", "volume": "3", "year": "2024" }, { "DOI": "10.1073/pnas.2304992120", "article-title": "H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic", "author": "Liu", "doi-asserted-by": "crossref", "first-page": "e2304992120", "journal-title": "Proc. Natl. Acad. Sci. USA", "key": "ref_78", "volume": "120", "year": "2023" }, { "DOI": "10.3389/fimmu.2018.01396", "doi-asserted-by": "crossref", "key": "ref_79", "unstructured": "Ströh, L.J., Nagarathinam, K., and Krey, T. (2018). Conformational flexibility in the CD81-binding site of the hepatitis C virus glycoprotein E2. Front. Immunol., 9." }, { "DOI": "10.1016/j.csbj.2023.03.029", "article-title": "Identifying promising druggable binding sites and their flexibility to target the receptor-binding domain of SARS-CoV-2 spike protein", "author": "Ghoula", "doi-asserted-by": "crossref", "first-page": "2339", "journal-title": "Comput. Struct. Biotechnol. J.", "key": "ref_80", "volume": "21", "year": "2023" }, { "DOI": "10.1038/s41429-021-00491-6", "article-title": "The mechanisms of action of ivermectin against SARS-CoV-2—An extensive review", "author": "Zaidi", "doi-asserted-by": "crossref", "first-page": "60", "journal-title": "J. Antibiot.", "key": "ref_81", "volume": "75", "year": "2022" }, { "DOI": "10.3390/ijms23052558", "doi-asserted-by": "crossref", "key": "ref_82", "unstructured": "Scheim, D.E. (2022). A deadly embrace: Hemagglutination mediated by SARS-CoV-2 spike protein at its 22 N-glycosylation sites, red blood cell surface sialoglycoproteins, and antibody. Int. J. Mol. Sci., 23." }, { "DOI": "10.3390/ijms242317039", "doi-asserted-by": "crossref", "key": "ref_83", "unstructured": "Scheim, D.E., Vottero, P., Santin, A.D., and Hirsh, A.G. (2023). Sialylated glycan bindings from SARS-CoV-2 spike protein to blood and endothelial cells govern the severe morbidities of COVID-19. Int. J. Mol. Sci., 24." }, { "DOI": "10.1016/j.bj.2024.100787", "doi-asserted-by": "crossref", "key": "ref_84", "unstructured": "Dima, F., Salvagno, G.L., and Lippi, G. (2024). Effects of recombinant SARS-CoV-2 spike protein variants on red blood cells parameters and red blood cell distribution width. Biomed. J., 47." } ], "reference-count": 84, "references-count": 84, "relation": {}, "resource": { "primary": { "URL": "https://www.mdpi.com/1999-4915/16/12/1836" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants", "type": "journal-article", "volume": "16" }
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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