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Validation of the binding affinities and stabilities of ivermectin and moxidectin against SARS-CoV-2 receptors using molecular docking and molecular dynamics simulation

Oranu et al., GSC Biological and Pharmaceutical Sciences, doi:10.30574/gscbps.2024.26.1.0030

Jan 2024

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Ivermectin for COVID-19

4th treatment shown to reduce risk in August 2020

^*, now with p < 0.00000000001 from 105 studies, recognized in 23 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.

4,500+ studies for 81 treatments. c19ivm.org

In Silico study showing that ivermectin and moxidectin bind strongly to SARS-CoV-2 viral targets including the main protease, helicase, and RNA polymerase. Binding was further validated through molecular dynamics simulations indicating stability of ivermectin and moxidectin complexes over 10ns. Authors suggest inhibition of viral replication and transcription by binding to the main protease, a key enzyme for these processes.

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, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, 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 system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.

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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.

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Oranu et al., 30 Jan 2024, peer-reviewed, 7 authors.

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

This Paper Ivermectin All

Validation of the binding affinities and stabilities of ivermectin and moxidectin against Sars-CoV-2 receptors using molecular docking and molecular dynamics simulation

Emmanuel Chuks Oranu, Esther Oluchukwu Eze, Adanna Ijeawele, Chisom George Obidimma, Belinda Chinecherem Umeh, Perpetua Chinonyelum Ejezie, Ic Uzochukwu

GSC Biological and Pharmaceutical Sciences, doi:10.30574/gscbps.2024.26.1.0030

Corona-viruses (CoVs), a large family of single-stranded RNA viruses, can infect animals and also humans, causing respiratory, gastrointestinal, hepatic, and neurologic disease. As the largest known RNA viruses, they are further divided into four genera: alpha-coronavirus, beta-corona-virus, gamma-corona virus and delta-coronavirus. SARS-CoV-2 belong to genus betacoronavirus. The viral genome of SARS-CoV-2 codes 4 major structural proteins: the nucleocapsid (N) protein, the transmembrane (M) protein, the envelope (E) protein, and the spike (S) protein. It also encodes 16 nonstructural proteins (NSPs) and 9 accessory proteins required for replication and pathogenesis. The Molecular docking simulations was used to determine the binding affinities of Ivermectin, Moxidectin and Molnupiravir against NSP13 receptor of SARS-CoV-2. The experimental crystal structures of the receptor was obtained from the protein data bank (PDB). The receptor was prepared using Chimera-1.10.1 and AutoDock tools-1.5.6. The 3D structure of the selected approved drugs and the reference ligand was obtained from PDB and Drugbank and prepared using AutoDock tools-1.5.6. Validation of docking protocol was done by reproducing the PDB crystal structures insilico. Molecular docking simulations were performed using AutoDockVina-4.2.6 on the Linux operating system (ubuntu) 20.04. Then the docking results were analysed and visualized using Pymol-2.3.0. Molecular dynamics of the frontrunners with the reference ligand and protein was done in 10000 ps. Moxidectin, molnupiravir and Ivermectin showed high binding affinities to the receptors. Moxidectin and Ivermectin showed stability after molecular dynamics simulation to further validate the claim. These drugs are predicted as possible antivirals in the treatment of Covid-19.

Flexibility Profile analysis Figure 6 RMSF Plot of the molecular dynamics simulation of the drug target and ligands Root Mean Square Fluctuation is a measure of the displacement of a particular atom or group of atoms, relative to the reference structure, averaged over the number of atoms. It is used for the analysis of time-dependent motions of the structures [14] . From the results in 7JIT, In the RMS fluctuation plot, the system was reasonably stable between 1500 atoms and 2000 atoms which indicates that above 2000 atoms, some amino acid residues caused fluctuation within the system with the least fluctuations between 800 atoms and 1800 atoms From the results in 7JKV,from point 1 atom to 2700 atoms the system was more stable than from point 2800 atoms to 3100 atoms. It can also be seen that Moxidectin exhibited better stability than Ivermectin. From the results in 5rlj,in the graph above, it can be deduced that there were a lot of fluctuations which might be due to the presence of amino acid residues in the system. However, there was still stability at points 3600 pico seconds to 4600 pico seconds. Compliance with ethical standards Disclosure of conflict of interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript. We certify that the submission is original work and is not under review at any other publication.

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{ 'indexed': {'date-parts': [[2024, 1, 30]], 'date-time': '2024-01-30T00:22:49Z', 'timestamp': 1706574169178}, 'reference-count': 0, 'publisher': 'GSC Online Press', 'issue': '1', 'content-domain': {'domain': ['www.gsconlinepress.com'], 'crossmark-restriction': False}, 'abstract': 'Corona-viruses (CoVs), a large family of single-stranded RNA viruses, can infect ' 'animals and also humans, causing respiratory, gastrointestinal, hepatic, and neurologic ' 'disease. As the largest known RNA viruses, they are further divided into four genera: ' 'alpha-coronavirus, beta- corona- virus, gamma-corona virus and delta-coronavirus. SARS-CoV-2 ' 'belong to genus betacoronavirus. The viral genome of SARS-CoV-2 codes 4 major structural ' 'proteins: the nucleocapsid (N) protein, the transmembrane (M) protein, the envelope (E) ' 'protein, and the spike (S) protein. It also encodes 16 nonstructural proteins (NSPs) and 9 ' 'accessory proteins required for replication and pathogenesis. The Molecular docking ' 'simulations was used to determine the binding affinities of Ivermectin, Moxidectin and ' 'Molnupiravir against NSP13 receptor of SARS-CoV-2. The experimental crystal structures of the ' 'receptor was obtained from the protein data bank (PDB). The receptor was prepared using ' 'Chimera-1.10.1 and AutoDock tools-1.5.6. The 3D structure of the selected approved drugs and ' 'the reference ligand was obtained from PDB and Drugbank and prepared using AutoDock ' 'tools-1.5.6. Validation of docking protocol was done by reproducing the PDB crystal ' 'structures insilico. Molecular docking simulations were performed using AutoDockVina-4.2.6 on ' 'the Linux operating system (ubuntu) 20.04. Then the docking results were analysed and ' 'visualized using Pymol-2.3.0. Molecular dynamics of the frontrunners with the reference ' 'ligand and protein was done in 10000 ps. Moxidectin, molnupiravir and Ivermectin showed high ' 'binding affinities to the receptors. Moxidectin and Ivermectin showed stability after ' 'molecular dynamics simulation to further validate the claim. These drugs are predicted as ' 'possible antivirals in the treatment of Covid-19.', 'DOI': '10.30574/gscbps.2024.26.1.0030', 'type': 'journal-article', 'created': {'date-parts': [[2024, 1, 29]], 'date-time': '2024-01-29T15:32:57Z', 'timestamp': 1706542377000}, 'page': '303-314', 'update-policy': 'http://dx.doi.org/10.30574/gscbps.ourcrossmarkpolicy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Validation of the binding affinities and stabilities of ivermectin and moxidectin against ' 'Sars-CoV-2 receptors using molecular docking and molecular dynamics simulation', 'prefix': '10.30574', 'volume': '26', 'author': [ {'family': 'Emmanuel Chuks Oranu', 'sequence': 'first', 'affiliation': []}, {'family': 'Esther Oluchukwu Eze', 'sequence': 'additional', 'affiliation': []}, {'family': 'Adanna Ijeawele', 'sequence': 'additional', 'affiliation': []}, {'family': 'Chisom George Obidimma', 'sequence': 'additional', 'affiliation': []}, {'family': 'Belinda Chinecherem Umeh', 'sequence': 'additional', 'affiliation': []}, {'family': 'Perpetua Chinonyelum Ejezie', 'sequence': 'additional', 'affiliation': []}, {'family': 'IC Uzochukwu', 'sequence': 'additional', 'affiliation': []}], 'member': '12033', 'published-online': {'date-parts': [[2024, 1, 30]]}, 'container-title': 'GSC Biological and Pharmaceutical Sciences', 'original-title': [], 'link': [ { 'URL': 'https://gsconlinepress.com/journals/gscbps/content/validation-binding-affinities-and-stabilities-ivermectin-and-moxidectin-against-sars-cov-2', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 1, 29]], 'date-time': '2024-01-29T15:32:58Z', 'timestamp': 1706542378000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://gsconlinepress.com/journals/gscbps/content/validation-binding-affinities-and-stabilities-ivermectin-and-moxidectin-against-sars-cov-2'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 1, 30]]}, 'references-count': 0, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 1, 30]]}}, 'URL': 'http://dx.doi.org/10.30574/gscbps.2024.26.1.0030', 'relation': {}, 'ISSN': ['2581-3250'], 'subject': ['Microbiology (medical)', 'Immunology', 'Immunology and Allergy'], 'container-title-short': 'GSC Biol. Pharm. Sci.', 'published': {'date-parts': [[2024, 1, 30]]}}

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