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All Studies   Meta Analysis    Recent:   

Computational Prediction of the Interaction of Ivermectin with Fibrinogen

Vottero et al., Molecular Sciences, doi:10.3390/ijms241411449
Jul 2023  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 100 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments. c19ivm.org
In Silico study showing that ivermectin may bind with high affinity to multiple sites on fibrinogen and may interfere with SARS-CoV-2 spike protein – fibrinogen binding, potentially inhibiting the formation of fibrin clots resistant to degradation (a hallmark of acute COVID-19 and long COVID).
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacterium which plays a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Vottero et al., 14 Jul 2023, peer-reviewed, 6 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Computational Prediction of the Interaction of Ivermectin with Fibrinogen
Paola Vottero, Scott Tavernini, Alessandro D Santin, David E Scheim, Jack A Tuszynski, Maral Aminpour
International Journal of Molecular Sciences, doi:10.3390/ijms241411449
Hypercoagulability and formation of extensive and difficult-to-lyse microclots are a hallmark of both acute COVID-19 and long COVID. Fibrinogen, when converted to fibrin, is responsible for clot formation, but abnormal structural and mechanical clot properties can lead to pathologic thrombosis. Recent experimental evidence suggests that the spike protein (SP) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly bind to the blood coagulation factor fibrinogen and induce structurally abnormal blood clots with heightened proinflammatory activity. Accordingly, in this study, we used molecular docking and molecular dynamics simulations to explore the potential activity of the antiparasitic drug ivermectin (IVM) to prevent the binding of the SARS-CoV-2 SP to fibrinogen and reduce the occurrence of microclots. Our computational results indicate that IVM may bind with high affinity to multiple sites on the fibrinogen peptide, with binding more likely in the central, E region, and in the coiled-coil region, as opposed to the globular D region. Taken together, our in silico results suggest that IVM may interfere with SP-fibrinogen binding and, potentially, decrease the formation of fibrin clots resistant to degradation. Additional in vitro studies are warranted to validate whether IVM binding to fibrinogen is sufficiently stable to prevent interaction with the SP, and potentially reduce its thrombo-inflammatory effect in vivo.
Author Contributions: Conceptualization, A.D.S., D.E.S. and M.A.; methodology, M.A., P.V. and S.T.; software, P.V., S.T. and M.A.; validation, M.A., P.V., S.T. and A.D.S.; formal analysis, P.V., S.T. and M.A.; investigation, P.V., S.T., M.A. and A.D.S.; resources, J.A.T. and M.A.; data curation, P.V. and S.T.; writing-original draft preparation, P.V. and S.T.; writing-review and editing, D.E.S., A.D.S., M.A., P.V., S.T. and J.A.T.; visualization, P.V. and S.T.; supervision, M.A., A.D.S., D.E.S. and J.A.T.; project administration, M.A. and J.A.T. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: A.D.S. reports grants from PUMA, grants from IMMUNOMEDICS, grants from GILEAD, grants from SYNTHON, grants and personal fees from MERCK, grants from BOEHINGER-INGELHEIM, grants from GENENTECH, grants and personal fees from TESARO, and grants and personal fees from EISAI. The other authors declare no conflict of interest. Abbreviations The The highest scoring pose of the SP in both states is illustrated in green, the second pose in blue, and the third in orange. The binding pockets where IVM inhibits fibrinogen, which happen to be situated at the interface of SP and fibrinogen, are emphasized as follows: Site 3 and Site 12, both located in the central E region, are highlighted in yellow and dark green, respectively. Meanwhile, the gamma1 site stands out in cyan, and the gamma2 site in purple; Site 3b, as identified by the Site..
References
Aminpour, Cannariato, Preto, Safaeeardebili, Moracchiato et al., Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds, doi:10.3390/computation10040051
Andrusier, Nussinov, Wolfson, Firedock, Fast Interaction Refinement in Molecular Docking, Proteins
Asakura, Ogawa, COVID-19-Associated Coagulopathy and Disseminated Intravascular Coagulation, Int. J. Hematol, doi:10.1007/s12185-020-03029-y
Barshtein, Wajnblum, Yedgar, Kinetics of Linear Rouleaux Formation Studied by Visual Monitoring of Red Cell Dynamic Organization, Biophys. J, doi:10.1016/S0006-3495(00)76791-9
Baskurt, Meiselman, Erythrocyte Aggregation: Basic Aspects and Clinical Importance, Clin. Hemorheol. Microcirc, doi:10.3233/CH-2012-1573
Becker, COVID-19 Update: COVID-19-Associated Coagulopathy, J. Thromb. Thrombolysis, doi:10.1007/s11239-020-02134-3
Berzuini, Bianco, Migliorini, Maggioni, Valenti et al., Red Blood Cell Morphology in Patients with COVID-19-Related Anaemia, Blood Transfus, doi:10.2450/2020.0242-20
Biondi, Gulati, Possick, Joseph, Singh et al., Unexplained dyspnea in a patient with a history of COVID-19, Chest, doi:10.1016/j.chest.2021.07.2054
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
Bullard, Chapter 41-CR3
Ceban, Ling, Lui, Lee, Gill et al., Fatigue and Cognitive Impairment in Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis, Brain Behav. Immun, doi:10.1016/j.bbi.2021.12.020
Couzin-Frankel, The Mystery of the Pandemic's 'Happy Hypoxia', Science, doi:10.1126/science.368.6490.455
Craddock, Mahajan, Spikes, Krishnamachary, Ram et al., Persistent Circulation of Soluble and Extracellular Vesicle-Linked Spike Protein in Individuals with Postacute Sequelae of COVID-19, J. Med. Virol, doi:10.1002/jmv.28568
Crump, Ivermectin: Enigmatic Multifaceted "wonder" Drug Continues to Surprise and Exceed Expectations, J. Antibiot, doi:10.1038/ja.2017.11
Darden, Duke, Giambasu, Gilson, Gohlke et al., None
Davalos, Akassoglou, Fibrinogen as a Key Regulator of Inflammation in Disease, Semin. Immunopathol, doi:10.1007/s00281-011-0290-8
Eberhardt, Santos-Martins, Tillack, Forli, AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings, J. Chem. Inf. Model, doi:10.1021/acs.jcim.1c00203
Edelsbrunner, Kirkpatrick, Seidel, On the Shape of a Set of Points in the Plane, IEEE Trans. Inf. Theory
Gattinoni, Coppola, Cressoni, Busana, Rossi et al., COVID-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome, Am. J. Respir. Crit. Care Med, doi:10.1164/rccm.202003-0817LE
González-Durruthy, Rial, Cordeiro, Liu, Ruso, Exploring the Conformational Binding Mechanism of Fibrinogen Induced by Interactions with Penicillin β-Lactam Antibiotic Drugs, J. Mol. Liq, doi:10.1016/j.molliq.2020.114667
González-Durruthy, Scanavachi, Rial, Liu, Cordeiro et al., Mapping the Underlying Mechanisms of Fibrinogen Benzothiazole Drug Interactions Using Computational and Experimental Approaches, Int. J. Biol. Macromol, doi:10.1016/j.ijbiomac.2020.07.044
Grobbelaar, Venter, Vlok, Ngoepe, Laubscher et al., SARS-CoV-2 Spike Protein S1 Induces Fibrin(Ogen) Resistant to Fibrinolysis: Implications for Microclot Formation in COVID-19, Biosci. Rep, doi:10.1042/BSR20210611
Gupta, Madhavan, Sehgal, Nair, Mahajan et al., Extrapulmonary Manifestations of COVID-19, Nat. Med, doi:10.1038/s41591-020-0968-3
Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects, J. Clin. Pharmacol, doi:10.1177/009127002237994
Huertas, Montani, Savale, Pichon, Tu et al., Endothelial Cell Dysfunction: A Major Player in SARS-CoV-2 Infection (COVID-19)?, Eur. Respir. J, doi:10.1183/13993003.01634-2020
Hysi, Saha, Kolios, Photoacoustic Ultrasound Spectroscopy for Assessing Red Blood Cell Aggregation and Oxygenation, J. Biomed. Opt, doi:10.1117/1.JBO.17.12.125006
Kell, Laubscher, Pretorius, A Central Role for Amyloid Fibrin Microclots in Long COVID/PASC: Origins and Therapeutic Implications, Biochem. J, doi:10.1042/BCJ20220016
Kibria, Hysi, Strohm, Kolios, Identification of Red Blood Cell Rouleaux Formation Using Photoacoustic Ultrasound Spectroscopy
Klotz, Ogbuokiri, Okonkwo, Ivermectin Binds Avidly to Plasma Proteins, Eur. J. Clin. Pharmacol, doi:10.1007/BF00316107
Klykov, Van Der Zwaan, Heck, Meijer, Scheltema, Missing Regions within the Molecular Architecture of Human Fibrin Clots Structurally Resolved by XL-MS and Integrative Structural Modeling, Proc. Natl. Acad. Sci, doi:10.1073/pnas.1911785117
Kollman, Pandi, Sawaya, Riley, Doolittle, Crystal Structure of Human Fibrinogen, Biochemistry, doi:10.1021/bi802205g
Lakhdari, Tabet, Boudraham, Laoussati, Aissanou et al., Red Blood Cells Injuries and Hypersegmented Neutrophils in COVID-19 Peripheral Blood Film, doi:10.1101/2020.07.24.20160101
Levi, Thachil, Iba, Levy, Coagulation Abnormalities and Thrombosis in Patients with COVID-19, Lancet Haematol, doi:10.1016/S2352-3026(20)30145-9
Li, Duan, Song, Xu, Comparative Study on the Interaction between Fibrinogen and Flavonoids, J. Mol. Struct, doi:10.1016/j.molstruc.2022.132963
Litvinov, Pieters, De Lange-Loots, Weisel, Fibrinogen, Macromolecular Protein Complexes III: Structure and Function
Liu, Tang, Pei, Zhang, Liu et al., Gastrodin Interaction with Human Fibrinogen: Anticoagulant Effects and Binding Studies, Chem. Eur. J, doi:10.1002/chem.200600549
Magro, Mulvey, Berlin, Nuovo, Salvatore et al., Complement Associated Microvascular Injury and Thrombosis in the Pathogenesis of Severe COVID-19 Infection: A Report of Five Cases, Transl. Res, doi:10.1016/j.trsl.2020.04.007
Marini, Gattinoni, Management of COVID-19 Respiratory Distress, JAMA, doi:10.1001/jama.2020.6825
Meiselman, Red Blood Cell Aggregation: 45 Years Being Curious, Biorheology, doi:10.3233/BIR-2009-0522
Melkumyants, Buryachkovskaya, Lomakin, Antonova, Serebruany, Mild COVID-19 and Impaired Blood Cell-Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?, Thromb. Haemost, doi:10.1055/a-1551-9911
Menter, Haslbauer, Nienhold, Savic, Hopfer et al., Postmortem Examination of COVID-19 Patients Reveals Diffuse Alveolar Damage with Severe Capillary Congestion and Variegated Findings in Lungs and Other Organs Suggesting Vascular Dysfunction, Histopathology, doi:10.1111/his.14134
Molyneux, Ward, Reflections on the Nobel Prize for Medicine 2015-The Public Health Legacy and Impact of Avermectin and Artemisinin, Trends Parasitol, doi:10.1016/j.pt.2015.10.008
Mondal, Lahiri, Deb, Bandyopadhyay, Shome et al., COVID-19: Are We Dealing with a Multisystem Vasculopathy in Disguise of a Viral Infection?, J. Thromb. Thrombolysis, doi:10.1007/s11239-020-02210-8
Navarro, Camprubí, Requena-Méndez, Buonfrate, Giorli et al., Safety of High-Dose Ivermectin: A Systematic Review and Meta-Analysis, J. Antimicrob. Chemother, doi:10.1093/jac/dkz524
O'boyle, Banck, James, Morley, Vandermeersch et al., Open Babel: An Open Chemical Toolbox, J. Cheminform, doi:10.1186/1758-2946-3-33
Ogata, Maley, Wu, Gilboa, Norman et al., Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease, doi:10.1093/clinchem/hvaa213
Patterson, Francisco, Yogendra, Long, Pise et al., Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection, doi:10.3389/fimmu.2021.746021
Picken, Fibrinogen Amyloidosis, The Clot Thickens! Blood, doi:10.1182/blood-2009-12-236810
Preto, Gentile, Assessing and improving the performance of consensus docking strategies using the DockBox package, J Comput. Aided Mol. Des, doi:10.1007/s10822-019-00227-7
Pretorius, Venter, Laubscher, Kotze, Oladejo et al., Prevalence of Symptoms, Comorbidities, Fibrin Amyloid Microclots and Platelet Pathology in Individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC), Cardiovasc. Diabetol, doi:10.1186/s12933-022-01579-5
Pretorius, Venter, Laubscher, Lourens, Steenkamp et al., Prevalence of Readily Detected Amyloid Blood Clots in 'Unclotted' Type 2 Diabetes Mellitus and COVID-19 Plasma: A Preliminary Report
Price, Mccabe, Garfield, Wort, Thrombosis and COVID-19 Pneumonia: The Clot Thickens! Eur, Respir. J, doi:10.1183/13993003.01608-2020
Prize, The 2015 Nobel Prize in Physiology or Medicine-Press Release
Rapkiewicz, Mai, Carsons, Pittaluga, Kleiner et al., Megakaryocytes and Platelet-Fibrin Thrombi Characterize Multi-Organ Thrombosis at Autopsy in COVID-19: A Case Series, doi:10.1016/j.eclinm.2020.100434
Ryu, Sozmen, Dixit, Montano, Matsui et al., SARS-CoV-2 Spike Protein Induces Abnormal Inflammatory Blood Clots Neutralized by Fibrin Immunotherapy, doi:10.1101/2021.10.12.464152
Sabioni, De Lorenzo, Lamas, Muccillo, Castro-Faria-Neto et al., Systemic Microvascular Endothelial Dysfunction and Disease Severity in COVID-19 Patients: Evaluation by Laser Doppler Perfusion Monitoring and Cytokine/Chemokine Analysis, Microvasc. Res, doi:10.1016/j.mvr.2020.104119
Santin, Scheim, Mccullough, Yagisawa, Borody et al., A Multifaceted Drug of Nobel Prize-Honored Distinction with Indicated Efficacy against a New Global Scourge, COVID-19, New Microbes New Infect, doi:10.1016/j.nmni.2021.100924
Scheim, 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
Schneidman-Duhovny, Inbar, Nussinov, Wolfson, PatchDock and SymmDock: Servers for Rigid and Symmetric Docking, Nucleic Acids Res, doi:10.1093/nar/gki481
Shafreen, Lakshmi, Pandian, Park, Kim et al., Unraveling the Antioxidant, Binding and Health-Protecting Properties of Phenolic Compounds of Beers with Main Human Serum Proteins: In Vitro and In Silico Approaches, Molecules, doi:10.3390/molecules25214962
Singh, Joseph, Heerdt, Cullinan, Lutchmansingh et al., Persistent Exertional Intolerance After COVID-19: Insights from Invasive Cardiopulmonary Exercise Testing, Chest, doi:10.1016/j.chest.2021.08.010
Soga, Shirai, Kobori, Hirayama, Use of Amino Acid Composition to Predict Ligand-Binding Sites, J. Chem. Inf. Model, doi:10.1021/ci6002202
Soriano, Murthy, Marshall, Relan, Diaz, A Clinical Case Definition of Post-COVID-19 Condition by a Delphi Consensus, Lancet Infect. Dis, doi:10.1016/S1473-3099(21)00703-9
Stubbs, Oschkinat, Mayr, Huber, Angliker et al., The Interaction of Thrombin with Fibrinogen. A structural basis for its specificity, Eur. J. Biochem, doi:10.1111/j.1432-1033.1992.tb16916.x
Swank, Senussi, Manickas-Hill, Yu, Li et al., Persistent Circulating SARS-CoC-2 Spike Is Associated with Post-Acute COVID-19 Sequelae, Clin. Infect. Dis, doi:10.1093/cid/ciac722
Syahbanu, Giriwono, Tjandrawinata, Suhartono, Molecular Docking of Subtilisin K2, a Fibrin-Degrading Enzyme from Indonesian Moromi, with Its Substrates, Food Sci. Technol. 2022, doi:10.1590/fst.61820
Valdés-Tresanco, Valdés-Tresanco, Valiente, Moreno, AMDock: A Versatile Graphical Tool for Assisting Molecular Docking with Autodock Vina and Autodock4, Biol. Direct, doi:10.1186/s13062-020-00267-2
Wagner, Steffen, Svetina, Aggregation of Red Blood Cells: From Rouleaux to Clot Formation, Comptes Rendus Phys, doi:10.1016/j.crhy.2013.04.004
Weisel, The Mechanical Properties of Fibrin for Basic Scientists and Clinicians, Biophys. Chem, doi:10.1016/j.bpc.2004.07.029
Wool, Miller, The Impact of COVID-19 Disease on Platelets and Coagulation, Pathobiology, doi:10.1159/000512007
Wygrecka, Birnhuber, Seeliger, Michalick, Pak et al., Altered Fibrin Clot Structure and Dysregulated Fibrinolysis Contribute to Thrombosis Risk in Severe COVID-19, Blood Adv, doi:10.1182/bloodadvances.2021004816
Yakovlev, Gorlatov, Ingham, Medved, Interaction of Fibrin(Ogen) with Heparin: Further Characterization and Localization of the Heparin-Binding Site, Biochemistry, doi:10.1021/bi0344073
Zhmurov, Protopopova, Litvinov, Zhukov, Weisel et al., Atomic Structural Models of Fibrin Oligomers, Structure, doi:10.1016/j.str.2018.04.005
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