All Studies Meta Analysis Recent:

Comparative Docking Studies on Curcumin with COVID-19 Proteins

Suravajhala et al., MDPI AG, doi:10.20944/preprints202005.0439.v3

Jun 2020

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Ivermectin for COVID-19

4th treatment shown to reduce risk in August 2020

^*, now with p < 0.00000000001 from 104 studies, recognized in 22 countries.

Lower risk for mortality, ventilation, ICU admission, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

4,300+ studies for 77 treatments. c19ivm.org

In Silico study reporting that ivermectin had the best affinity towards all targeted proteins and showed efficient binding to non-structural proteins.

68 preclinical studies support the efficacy of ivermectin for COVID-19:

30 In Silico studies1-30

24 In Vitro studies31-54

14 In Vivo animal studies41,47,54-65

Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.

Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CL^pro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,78, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system79, has immunomodulatory46 and anti-inflammatory65,80 properties, and has an extensive and very positive safety profile81.

Important missing comments or errors? Let us know.

Study covers ivermectin and curcumin.

1. de Oliveira Só et al., In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease, MDPI AG, doi:10.20944/preprints202404.1825.v1.preprints.org, doi.org.

2. Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.scienceopen.com, doi.org.

3. Oranu et al., Validation of the binding affinities and stabilities of ivermectin and moxidectin against SARS-CoV-2 receptors using molecular docking and molecular dynamics simulation, GSC Biological and Pharmaceutical Sciences, doi:10.30574/gscbps.2024.26.1.0030.gsconlinepress.com, doi.org.

4. Zhao et al., Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis, Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752.frontiersin.org, doi.org.

5. Vottero et al., Computational Prediction of the Interaction of Ivermectin with Fibrinogen, Molecular Sciences, doi:10.3390/ijms241411449.mdpi.com, doi.org.

6. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.sciencedirect.com, doi.org.

7. Umar et al., Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach, Jurnal Teknologi Laboratorium, doi:10.29238/teknolabjournal.v11i1.344.teknolabjournal.com, doi.org.

8. Alvarado et al., Interaction of the New Inhibitor Paxlovid (PF-07321332) and Ivermectin With the Monomer of the Main Protease SARS-CoV-2: A Volumetric Study Based on Molecular Dynamics, Elastic Networks, Classical Thermodynamics and SPT, Computational Biology and Chemistry, doi:10.1016/j.compbiolchem.2022.107692.sciencedirect.com, doi.org.

9. Aminpour et al., In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds, Computation, doi:10.3390/computation10040051.mdpi.com, doi.org.

10. Parvez et al., Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host–pathogen interaction, pathogenicity, and possible drug therapeutics, Immunity, Inflammation and Disease, doi:10.1002/iid3.639.wiley.com, doi.org.

11. Francés-Monerris et al., Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection, Physical Chemistry Chemical Physics, doi:10.1039/D1CP02967C.rsc.org, doi.org.

12. González-Paz et al., Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach, Biophysical Chemistry, doi:10.1016/j.bpc.2021.106677.sciencedirect.com, doi.org.

13. González-Paz (B) et al., Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models, Journal of Molecular Liquids, doi:10.1016/j.molliq.2021.117284.sciencedirect.com, doi.org.

14. Rana et al., A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection, Research Square, doi:10.21203/rs.3.rs-755838/v1.researchsquare.com, doi.org.

15. Muthusamy et al., Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein, Journal of Virology & Antiviral Research, www.scitechnol.com/abstract/virtual-screening-reveals-potential-antiparasitic-drugs-inhibiting-the-receptor-binding-domain-of-sarscov2-spike-protein-16398.html.scitechnol.com.

16. Qureshi et al., Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750.tandfonline.com, doi.org.

17. Schöning et al., Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains, Research Square, doi:10.21203/rs.3.rs-379291/v1.researchsquare.com, doi.org.

18. Bello et al., Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1911857.tandfonline.com, doi.org.

19. Udofia et al., In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV, Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2.springer.com, doi.org.

20. Choudhury et al., Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach, Future Medicine, doi:10.2217/fvl-2020-0342.futuremedicine.com, doi.org.

21. Kern et al., Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing, Frontiers in Pharmacology, doi:10.3389/fphar.2021.625678.frontiersin.org, doi.org.

22. Saha et al., The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2, Structural Chemistry, doi:10.1007/s11224-021-01776-0.researchsquare.com, doi.org.

23. Eweas et al., Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2, Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908.frontiersin.org, doi.org.

24. Parvez (B) et al., Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach, International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.098.sciencedirect.com, doi.org.

25. Francés-Monerris (B) et al., Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent, ChemRxiv, doi:10.26434/chemrxiv.12782258.v1.chemrxiv.org, doi.org.

26. Kalhor et al., Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1824816.tandfonline.com, doi.org.

27. Swargiary, A., Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies, Research Square, doi:10.21203/rs.3.rs-73308/v1.researchsquare.com, doi.org.

28. Maurya, D., A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients, American Chemical Society (ACS), doi:10.26434/chemrxiv.12630539.v1.chemrxiv.org, doi.org.

29. Lehrer et al., Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2, In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134.iiarjournals.org, doi.org.

30. Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, MDPI AG, doi:10.20944/preprints202005.0439.v3.preprints.org, doi.org.

31. Shahin et al., The selective effect of Ivermectin on different human coronaviruses; in-vitro study, Research Square, doi:10.21203/rs.3.rs-4180797/v1.researchsquare.com, doi.org.

32. Jitobaom et al., Identification of inositol monophosphatase as a broad‐spectrum antiviral target of ivermectin, Journal of Medical Virology, doi:10.1002/jmv.29552.wiley.com, doi.org.

33. Fauquet et al., Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction, Molecules, doi:10.3390/molecules28248072.mdpi.com, doi.org.

34. García-Aguilar et al., In Vitro Analysis of SARS-CoV-2 Spike Protein and Ivermectin Interaction, International Journal of Molecular Sciences, doi:10.3390/ijms242216392.mdpi.com, doi.org.

35. Liu et al., SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes, Stem Cell Research & Therapy, doi:10.1186/s13287-023-03485-3.biomedcentral.com, doi.org.

36. Boschi et al., SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects, bioRxiv, doi:10.1101/2022.11.24.517882.biorxiv.org, doi.org.

37. De Forni et al., Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients, PLoS ONE, doi:10.1371/journal.pone.0276751.plos.org, doi.org.

38. Saha (B) et al., Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder, Pharmaceutics, doi:10.3390/pharmaceutics14071432.mdpi.com, doi.org.

39. Jitobaom (B) et al., Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations, BMC Pharmacology and Toxicology, doi:10.1186/s40360-022-00580-8.biomedcentral.com, doi.org.

40. Croci et al., Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin, International Journal of Biomaterials, doi:10.1155/2016/8043983.hindawi.com, doi.org.

41. Zheng et al., Red blood cell-hitchhiking mediated pulmonary delivery of ivermectin: Effects of nanoparticle properties, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121719.sciencedirect.com, doi.org.

42. Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.mdpi.com, doi.org.

43. Liu (B) et al., Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human pluripotent stem cell-derived cardiomyocytes, Stem Cell Reports, doi:10.1016/j.stemcr.2022.01.014.sciencedirect.com, doi.org.

44. Segatori et al., Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients, Viruses, doi:10.3390/v13102084.mdpi.com, doi.org.

45. Jitobaom (C) et al., Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-941811/v1.researchsquare.com, doi.org.

46. Munson et al., Niclosamide and ivermectin modulate caspase-1 activity and proinflammatory cytokine secretion in a monocytic cell line, British Society For Nanomedicine Early Career Researcher Summer Meeting, 2021, web.archive.org/web/20230401070026/https://michealmunson.github.io/COVID.pdf.archive.org.

47. Mountain Valley MD, Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™, www.globenewswire.com/en/news-release/2021/05/18/2231755/0/en/Mountain-Valley-MD-Receives-Successful-Results-From-BSL-4-COVID-19-Clearance-Trial-on-Three-Variants-Tested-With-Ivectosol.html.globenewswire.com.

48. Yesilbag et al., Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro, Virus Research, doi:10.1016/j.virusres.2021.198384.sciencedirect.com, doi.org.

49. Mody et al., Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents, Communications Biology, doi:10.1038/s42003-020-01577-x.nature.com, doi.org.

50. Jeffreys et al., Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2, International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542.sciencedirect.com, doi.org.

51. Surnar et al., Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19, ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179.acs.org, doi.org.

52. Li et al., Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment, J. Cellular Physiology, doi:10.1002/jcp.30055.wiley.com, doi.org.

53. Caly et al., The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research, doi:10.1016/j.antiviral.2020.104787.sciencedirect.com, doi.org.

54. Zhang et al., Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflammation Research, doi:10.1007/s00011-008-8007-8.springer.com, doi.org.

55. Gao et al., Ivermectin ameliorates acute myocarditis via the inhibition of importin-mediated nuclear translocation of NF-κB/p65, International Immunopharmacology, doi:10.1016/j.intimp.2024.112073.sciencedirect.com, doi.org.

56. Abd-Elmawla et al., Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis, Journal of Zhejiang University-SCIENCE B, doi:10.1631/jzus.B2200385.springer.com, doi.org.

57. Uematsu et al., Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model, The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0.nature.com, doi.org.

58. Albariqi et al., Pharmacokinetics and Safety of Inhaled Ivermectin in Mice as a Potential COVID-19 Treatment, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121688.sciencedirect.com, doi.org.

59. Errecalde et al., Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model, Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017.sciencedirect.com, doi.org.

60. Madrid et al., Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation, Heliyon, doi:10.1016/j.heliyon.2020.e05820.sciencedirect.com, doi.org.

61. Ma et al., Ivermectin contributes to attenuating the severity of acute lung injury in mice, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113706.sciencedirect.com, doi.org.

62. de Melo et al., Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin, EMBO Mol. Med., doi:10.15252/emmm.202114122.embopress.org, doi.org.

63. Arévalo et al., Ivermectin reduces in vivo coronavirus infection in a mouse experimental model, Scientific Reports, doi:10.1038/s41598-021-86679-0.nature.com, doi.org.

64. Chaccour et al., Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats, Scientific Reports, doi:10.1038/s41598-020-74084-y.nature.com, doi.org.

65. Yan et al., Anti-inflammatory effects of ivermectin in mouse model of allergic asthma, Inflammation Research, doi:10.1007/s00011-011-0307-8.springer.com, doi.org.

66. Götz et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Scientific Reports, doi:10.1038/srep23138.nature.com, doi.org.

67. Tay et al., Nuclear localization of dengue virus (DENV) 1–4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antiviral Research, doi:10.1016/j.antiviral.2013.06.002.sciencedirect.com, doi.org.

68. Wagstaff et al., Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochemical Journal, doi:10.1042/BJ20120150.portlandpress.com, doi.org.

69. Wagstaff (B) et al., An AlphaScreen®-Based Assay for High-Throughput Screening for Specific Inhibitors of Nuclear Import, SLAS Discovery, doi:10.1177/1087057110390360.sciencedirect.com, doi.org.

70. Barrows et al., A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection, Cell Host & Microbe, doi:10.1016/j.chom.2016.07.004.sciencedirect.com, doi.org.

71. Yang et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral Research, doi:10.1016/j.antiviral.2020.104760.sciencedirect.com, doi.org.

72. Mastrangelo et al., Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dks147.oup.com, doi.org.

73. Varghese et al., Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses, Antiviral Research, doi:10.1016/j.antiviral.2015.12.012.sciencedirect.com, doi.org.

74. Bennett et al., Role of a nuclear localization signal on the minor capsid Proteins VP2 and VP3 in BKPyV nuclear entry, Virology, doi:10.1016/j.virol.2014.10.013.sciencedirect.com, doi.org.

75. Kosyna et al., The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biological Chemistry, doi:10.1515/hsz-2015-0171.degruyter.com, doi.org.

76. Scheim et al., Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19, International Journal of Molecular Sciences, doi:10.3390/ijms242317039.mdpi.com, doi.org.

77. Liu (C) et al., Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury, Frontiers in Immunology, doi:10.3389/fimmu.2023.1324021.frontiersin.org, doi.org.

78. DiNicolantonio et al., Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19, Open Heart, doi:10.1136/openhrt-2020-001350.bmj.com, doi.org.

79. Hazan et al., Treatment with Ivermectin Increases the Population of Bifidobacterium in the Gut, ACG 2023, acg2023posters.eventscribe.net/posterspeakers.asp.eventscribe.net.

80. DiNicolantonio (B) et al., Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors, Open Heart, doi:10.1136/openhrt-2021-001655.bmj.com, doi.org.

81. Descotes, J., Medical Safety of Ivermectin, ImmunoSafe Consultance, web.archive.org/web/20240313025927/https://www.medincell.com/wp-content/uploads/2021/03/Clinical_Safety_of_Ivermectin-March_2021.pdf.archive.org.

Suravajhala et al., 7 Jun 2020, preprint, 8 authors. Contact: giri@genomixbiotech.com (corresponding author), prash@bisr.res.in.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Ivermectin All

Comparative Docking Studies on Curcumin with COVID-19 Proteins

Renuka Suravajhala, Abhinav Parashar, Babita Malik, Viswanathan Arun Nagaraj, Govindarajan Padmanaban, P B Kavi Kishor, Rathnagiri Polavarapu, Prashanth Suravajhala

doi:10.20944/preprints202005.0439.v3

Highlights 1. Our findings confirm the role of Q163 aminoacid site for potential tethered site or target which is in agreement with ivermectin, the best possible and known drug. 2. We have employed a rigorous strategy in screening the docking complexes from a majority of hypothetical genes or orphan open reading frames, structural and non-structural proteins. 3. We believe that the findings presented in our paper will appeal to researchers working on COVID-19, particularly those interested to characteristically screen docking complexes.

Author contributions: GP, PBK and RP ideated the project. RS and AP jointly analysed the structures and modelled the docking complexes. PS performeddid the protein interaction analyses. AP and RS wrote the first draft with PS, PBK, BM and RP. GP, PBK, PS, VAN and RP proofread the manuscript. Competing interests: None

References

Balasco, Esposito, De Simone, Vitagliano, Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms, Protein Sci, doi:10.1002/pro.2279

Bosch, Van Der Zee, De Haan, Rottier, The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex, J. Virol, doi:10.1128/jvi.77.16.8801-8811.2003

Bouvet, Lugari, Posthuma, Coronavirus Nsp10, a critical co-factor for activation of multiple replicative enzymes, J Biol Chem, doi:10.1074/jbc.M114.577353

Chen, Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2′-O-methylation by nsp16/nsp10 protein complex, PLOS Pathog, doi:10.1371/journal.ppat.1002294

Chen, Liu, Guo, Emerging coronaviruses: Genome structure, replication, and pathogenesis, Journal of Medical Virology, doi:10.1002/jmv.25681

Delano, The PyMOL Molecular Graphics System; DeLano Scientific

Dende, Meena, Nagarajan, Nagaraj, Panda et al., Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria, Scientific reports, doi:10.1038/s41598-017-10672-9

Dolati, Ahmadi, Aghebti-Maleki, Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators, Pharmacol Rep, doi:10.1016/j.pharep.2018.05.008

Hesari, Ghasemi, Salarinia, Biglari, Tabar Molla Hassan et al., Effects of curcumin on NF-κB, AP-1, and Wnt/β-catenin signaling pathway in hepatitis B virus infection, Journal of cellular biochemistry, doi:10.1002/jcb.26829

Hilgenfeld, Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites, Acta Pharm. Sin. B, doi:10.1111/febs.12936Kang

Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052

Kang, Yang, Hong, Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

Mcbride, Van Zyl, Fielding, The coronavirus nucleocapsid is a multifunctional protein, Viruses, doi:10.3390/v6082991

Morris, AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J. Comput. Chem, doi:10.1002/jcc.21256

N M O'boyle, Banck, James, Morley, Vandermeersch et al., Open Babel: An open chemical toolbox, J. Cheminf, doi:10.1186/1758-2946-3-33

Nelson, Dahlin, Bisson, Graham, Pauli et al., The essential medicinal chemistry of curcumin: miniperspective, Journal of medicinal chemistry, doi:10.1021/acs.jmedchem.6b00975

Padmanaban, Nagaraj, Curcumin from turmeric as an adjunct drug?, Chem, doi:10.1016/B978-0-444-64057-4.00006-5

Padmanaban, Nagaraj, Curcumin may defy medicinal chemists, ACS Med. Chem. Lett, doi:10.1021/acsmedchemlett.7b00051

Pettersen, Goddard, Huang, Couch, Greenblatt et al., UCSF Chimera -A Visualization System for Exploratory Research and Analysis, J. Comput. Chem

Prasad, Tyagi, Aggarwal, Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice, Cancer Res. Treat. Off. J. Korean Cancer Assoc, doi:10.4143/crt.2014.46.1.2

Rossi, Sanga, Barton, Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients, Elife, doi:10.7554/eLife.57278

Sampangi-Ramaiah, Vishwakarma, Shaanker, Molecular docking analysis of selected natural products from plants for inhibition of SARS-CoV-2 main protease, Current Science

Soleimani, Sahebkar, Hosseinzadeh, Turmeric (Curcuma longa) and its major constituent (Curcumin) as nontoxic and safe substances: Review, Phytother. Res, doi:10.1002/ptr.6054

Su, Lou, Sun, Zhai, Yang et al., Dodecamer structure of severe acute respiratory syndrome coronavirus nonstructural protein nsp10, Journal of Virology, doi:10.1128/JVI.00483-06

Vathsala, Dende, Nagaraj, Bhattacharya, Das et al., Curcuminarteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation, PLoS One, doi:10.1371/journal.pone.0029442

Walls, Park, Tortorici, Wall, Mcguire et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Cell, doi:10.1016/j.cell.2020.02.058

Walls, Tortorici, Snijder, Xiong, Bosch et al., Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.1708727114

Xia, Ye, Shi, Zhou, Hua, Curcumin improves diabetes mellitus-associated cerebral infarction by increasing the expression of GLUT1 and GLUT3, Molecular medicine reports, doi:10.3892/mmr.2017.8085

Yang, Lee, Si, Lee, You et al., Curcumin shows antiviral properties against norovirus, Molecules, doi:10.3390/molecules21101401

Zhou, Liu, Wang, Liu, Li et al., The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha, Journal of Virology, doi:10.1128/JVI.00133-08

{ 'indexed': {'date-parts': [[2023, 2, 5]], 'date-time': '2023-02-05T05:24:08Z', 'timestamp': 1675574648871}, 'posted': {'date-parts': [[2020, 6, 7]]}, 'group-title': 'LIFE SCIENCES', 'reference-count': 0, 'publisher': 'MDPI AG', 'license': [ { 'start': { 'date-parts': [[2020, 6, 7]], 'date-time': '2020-06-07T00:00:00Z', 'timestamp': 1591488000000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2020, 6, 5]]}, 'abstract': 'Corona virus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory ' 'Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive strand RNA virus. The SARS-CoV-2 ' 'genome and its association to SAR-CoV-1 vary from ca. 66% to 96% depending on the type of ' 'betacoronavirdeae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ' 'ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has ' 'been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a ' 'natural bioactive molecule has been shown to have a therapeutic potential for various ' 'diseases, but its effect on COVID-19 has not been explored. In this study, we show the ' 'binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike ' 'glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane ' 'glycoprotein (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase ' '(PDB ID: 6M71) structures. Our results indicate that curcumin has high binding affinity ' 'towards nucleocapsid and nsp 10 proteins with potential antiviral activity.', 'DOI': '10.20944/preprints202005.0439.v3', 'type': 'posted-content', 'created': {'date-parts': [[2020, 6, 8]], 'date-time': '2020-06-08T15:31:31Z', 'timestamp': 1591630291000}, 'source': 'Crossref', 'is-referenced-by-count': 4, 'title': 'Comparative Docking Studies on Curcumin with COVID-19 Proteins', 'prefix': '10.20944', 'author': [ {'given': 'Renuka', 'family': 'Suravajhala', 'sequence': 'first', 'affiliation': []}, {'given': 'Abhinav', 'family': 'Parashar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Babita', 'family': 'Malik', 'sequence': 'additional', 'affiliation': []}, {'given': 'Viswanathan Arun', 'family': 'Nagaraj', 'sequence': 'additional', 'affiliation': []}, {'given': 'Govindarajan', 'family': 'Padmanaban', 'sequence': 'additional', 'affiliation': []}, {'given': 'PB', 'family': 'Kavi Kishor', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rathnagiri', 'family': 'Polavarapu', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-8535-278X', 'authenticated-orcid': False, 'given': 'Prashanth', 'family': 'Suravajhala', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'container-title': [], 'original-title': [], 'deposited': { 'date-parts': [[2020, 6, 8]], 'date-time': '2020-06-08T15:44:10Z', 'timestamp': 1591631050000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.preprints.org/manuscript/202005.0439/v3'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 6, 7]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.20944/preprints202005.0439.v3', 'relation': { 'is-version-of': [ { 'id-type': 'doi', 'id': '10.20944/preprints202005.0439.v1', 'asserted-by': 'subject'}, { 'id-type': 'doi', 'id': '10.20944/preprints202005.0439.v2', 'asserted-by': 'subject'}], 'has-version': [ { 'id-type': 'doi', 'id': '10.20944/preprints202005.0439.v1', 'asserted-by': 'object'}, { 'id-type': 'doi', 'id': '10.20944/preprints202005.0439.v2', 'asserted-by': 'object'}]}, 'published': {'date-parts': [[2020, 6, 7]]}, 'subtype': 'preprint'}

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ 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. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0