Conv. Plasma
Nigella Sativa
Peg.. Lambda

All HCQ studies
Meta analysis
Home COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  

A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity

Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892
Aug 2020  
  Source   PDF   All Studies   Meta AnalysisMeta
In Vitro study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance of accurate dosing. Metabolic analysis revealed HCQ/CQ inhibit oxidative phosphorylation in mitochondria (likely by sequestering protons needed to drive ATP synthase), inhibiting infection and/or slowing replication.
Sheaff et al., 2 Aug 2020, preprint, 1 author.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperHCQAll
A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity
Robert J Sheaff
Chloroquine and hydroxychloroquine (H)CQ are well known anti-malarial drugs, while their use against COVID-19 is more controversial. (H)CQ activity was examined in tissue culture cells to determine if their anti-viral benefits or adverse effects might be due to altering host cell pathways. Metabolic analysis revealed (H)CQ inhibit oxidative phosphorylation in mitochondria, likely by sequestering protons needed to drive ATP synthase. This activity could cause cardiotoxicity because heart muscle relies on beta oxidation of fatty acids. However, it might also explain their therapeutic benefit against COVID-19. A new model of SARS-CoV-2 infection postulates virus enters host cell mitochondria and uses its protons for genome release. Oxidative phosphorylation is eventually compromised, so glycolysis is upregulated to maintain ATP levels. (H)CQ could prevent viral infection and/or slow its replication by sequestering these protons. In support of this model other potential COVID-19 therapeutics also targeted mitochondria, as did tobacco smoke, which may underlie smokers' protection. The mitochondria of young people are naturally more adaptable and resilient, providing a rationale for their resistance to disease progression. Conversely, obesity and diabetes could exacerbate disease severity by providing extra glucose to infected cells dependent on glycolysis. The description of (H)CQ function presented here, together with its implications for understanding SARS-CO-V2 infection, makes testable predictions about disease progression and identifies new approaches for treating COVID-19. .
Smoke exposure Four p60mm plates of attached A549 lung carcinoma cells were aspirated, washed with PBS, and aspirated again. Control plates were untreated and exposed to breath exhalation in the absence of smoke. Cigar smoke was blown into two experimental plates followed by rapid lid closure to trap the smoke. After 3min. at room temperature the lid was removed from one plate and smoke allowed to dissipate (labeled 1 smoke in Figure 4G ). The other plate was exposed to another aliquot of cigar smoke followed by rapid lid closure (labeled 2 smoke). After 6 min. total incubation time cells were removed with trypsin, pelleted, and re-suspended in 500L of the indicated media. 100l aliquots were distributed in a white 96 well assay plate and incubated at 37 o C in the CO2 incubator for 1hr. ATP levels were then analyzed using CellTiterGlo as described previously. Competing interests The author declares no competing interests. Materials & Correspondence Robert J. Sheaff Associate Professor The University of Tulsa Department of Chemistry and Biochemistry Keplinger M2215 800 South Tucker Drive Tulsa, OK 74104 Office 918-631-2319 E-mail: Sheaff, 2020 Supl. Fig. 4 Supl. Fig. 5 : Red blood cells were pre-incubated with 1mM CQ for 1hr (orange line). After washing an aliquot was withdrawn to determine ATP levels using CTG (inset graph). Remaining cells were lysed by re-suspending in H2O and vortexing, followed by UV/Vis analysis of the..
Alifano, Alifano, Forgez, Iannelli, Renin-angiotensin system at the heart of COVID-19 pandemic, Biochimie, doi:10.1016/j.biochi.2020.04.008
Clayton, Shadel, Isolation of Mitochondria from Tissue Culture Cells, doi:10.1101/pdb.prot080002
Dowd, Andriano, Brazel, Rotondi, Block et al., Demographic science aids in understanding the spread and fatality rates of COVID-19, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2004911117
Felsenstein, Herbert, Mcnamara, Hedrich, COVID-19: Immunology and treatment options, Clin Immunol, doi:10.1016/j.clim.2020.108448
Ferner, Aronson, Chloroquine and hydroxychloroquine in covid-19, BMJ, doi:10.1136/bmj.m1432
Fitch, Involvement of heme in the antimalarial action of chloroquine, Trans Am Clin Climatol Assoc
Guzik, COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options, Cardiovasc Res, doi:10.1093/cvr/cvaa106
Hussain, Bhowmik, Do, Moreira, COVID-19 and diabetes: Knowledge in progress, Diabetes Res Clin Pract, doi:10.1016/j.diabres.2020.108142
Janowitz, Gablenz, Pattinson, Wang, Conigliaro et al., Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series, Gut, doi:10.1136/gutjnl-2020-321852
Kase, Nikolić, Bakke, Bogen, Aas et al., Remodeling of Oxidative Energy Metabolism by Galactose Improves Glucose Handling and Metabolic Switching in Human Skeletal Muscle Cells, PLoS One, doi:10.1371/journal.pone.0059972
Kashani, Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes, Mayo Clin Proc, doi:10.1016/j.mayocp.2020.04.021
Kolwicz, Purohit, Tian, Cardiac Metabolism and its Interactions with Contraction, Growth, and Survival of Cardiomyocytes, Circulation Research, doi:10.1161/CIRCRESAHA.113.302095
Magagnoli, Narendran, Pereira, Cummings, Hardin et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, MedRxiv, doi:.10.1101/2020.04.16.20065920
Malik, Properties of Coronavirus and SARS-CoV-2, Malays J Pathol
Moore, Chloroquine for COVID-19 Infection, Drug Saf, doi:10.1007/s40264-020-00933-4
Osellame, Blacker, Duchen, Cellular and molecular mechanisms of mitochondrial function, Best Pract Res Clin Endocrinol Metab, doi:10.1016/j.beem.2012.05.003
Pajak, Siwiak, Sołtyka, Priebe, Zieliński et al., 2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents, Int J Mol Sci, doi:10.3390/ijms21010234
Park, Epidemiology, Virology, and Clinical Features of Severe Acute Respiratory Syndromecoronavirus-2 (SARS-CoV-2
Remington, Powell, Clozapine and COVID-19, J Psychiatry Neurosci, doi:10.1503/jpn.2045301
Schrezenmeier, Dörner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol, doi:10.1038/s41584-020-0372-x
Slater, Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum, Pharmacol Ther, doi:10.1016/0163-7258(93)90056-j
Sun, Youle, Finkel, The Mitochondrial Basis of Aging, Mol Cell, doi:10.1016/j.molcel.2016.01.028
Vardavas, Nikitara, COVID-19 and smoking: A systematic review of the evidence, Tob Induc Dis, doi:10.18332/tid/119324
Vial, Detaille, Guigas, Role of Mitochondria in the Mechanism(s) of Action of Metformin, Front Endocrinol, doi:10.3389/fendo.2019.00294
Walls, Park, Tortorici, Wall, Mcguire et al., Structure, Function, and Antigenicity of the SARS-CoV-2 Glycoprotein, Cell, doi:10.1016/j.cell.2020.02.058
Weiss, Leibowitz, Coronavirus pathogenesis, Adv Virus Res, doi:10.1016/B978-0-12-385885-6.00009-2
Xue, Moyer, Peng, Wu, Hannafon et al., Chloroquine is a zinc ionophore, PLoS One, doi:10.1371/journal.pone.0109180
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, 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. FLCCC and WCH provide treatment protocols.
  or use drag and drop