Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients

Maurya, D., American Chemical Society (ACS), doi:10.26434/chemrxiv.12630539.v1
Jul 2020  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
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 a combination of ivermectin and doxycycline may inhibit SARS-CoV-2 infection through binding to multiple viral proteins as well as the host ACE2 receptor. Authors suggest that ivermectin may block viral entry by interfering with spike protein binding to ACE2, while both compounds could inhibit viral replication by targeting the RNA-dependent RNA polymerase and other proteins involved in immune system evasion. Additionally, doxycycline may provide anti-inflammatory and antiviral effects. The binding affinities and stability of the compound-protein complexes indicate promising potential for this drug combination in COVID-19 treatment and prevention.
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.
Maurya et al., 9 Jul 2020, preprint, 1 author. Contact: dkmaurya@barc.gov.in, dkmauryabarc@gmail.com.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients
Ph.D Dharmendra Kumar Maurya
The current outbreak of the corona virus disease 2019 , has affected almost entire world and become pandemic now. Currently, there is neither any FDA approved drugs nor any vaccines available to control it. Very recently in Bangladesh, a group of doctors reported astounding success in treating patients suffering from COVID-19 with two commonly used drugs, Ivermectin and Doxycycline. In the current study we have explored the possible mechanism by which these drugs might have worked for the positive response in the COVID-19 patients. To explore the mechanism we have used molecular docking and molecular dynamics simulation approach. Effectiveness of Ivermectin and doxycycline were evaluated against Main Protease (Mpro), Spike (S) protein, Nucleocapsid (N), RNA-dependent RNA polymerase (RdRp, NSP12), ADP Ribose Phosphatase (NSP3), Endoribonuclease (NSP15) and methyltransferase (NSP10-NSP16 complex) of SARS-CoV-2 as well as human angiotensin converting enzyme 2 (ACE2) receptor. Our study shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the Spike-RBD and ACE2 interacting region indicating that it might be interfering in the interaction of spike with ACE2 and preventing the viral entry in to the host cells. Ivermectin also exhibited significant binding affinity with different SARS-CoV-2 structural and non-structural proteins (NSPs) which have diverse functions in virus life cycle. Significant binding of Ivermectin with RdRp indicate its role in the inhibition of the viral replication and ultimately impeding the multiplication of the virus. Ivermectin also possess significant binding affinity with NSP3, NSP10, NSP15 and NSP16 which helps virus in escaping from host immune system. Molecular dynamics simulation study shows that binding of the Ivermectin with Mpro, Spike, NSP3, NSP16 and ACE2 was quiet stable. Thus, our docking and simulation studies reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition of viral entry and enhance viral load clearance by targeting various viral functional proteins.
Declaration of Conflicting Interests The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References
Abraham, Murtola, Schulz, Páll, Smith et al., GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, doi:10.1016/j.softx.2015.06.001
Aggarwal, Jain, Talapatra, Yadav, Gupta et al., Evaluation of role of doxycycline (a matrix metalloproteinase inhibitor) on renal functions in patients of diabetic nephropathy, Ren Fail, doi:10.3109/0886022x.2010.502606
Bhardwaj, Liu, Leibowitz, Kao, The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein, Journal of virology, doi:10.1128/JVI.07012-11
Buonfrate, Salas-Coronas, Muñoz, Maruri, Rodari et al., Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(19)30289-0
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research, doi:10.1016/j.antiviral.2020.104787
Caly, Wagstaff, Jans, Nuclear trafficking of proteins from RNA viruses: Potential target for antivirals?, Antiviral Research, doi:10.1016/j.antiviral.2012.06.008
Dallakyan, Olson, Small-molecule library screening by docking with PyRx, Methods Mol Biol, doi:10.1007/978-1-4939-2269-7_19
Egloff, Ferron, Campanacci, Longhi, Rancurel et al., The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world, Proceedings of the National Academy of Sciences of the United States of America, doi:10.1073/pnas.0307877101
González Canga, Sahagún Prieto, Diez Liébana, Fernández Martínez, Sierra et al., The Pharmacokinetics and Interactions of Ivermectin in Humans-A Mini-review, The AAPS Journal, doi:10.1208/s12248-007-9000-9
Götz, Magar, Dornfeld, Giese, Pohlmann et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Scientific reports, doi:10.1038/srep23138
He, Marneros, Doxycycline inhibits polarization of macrophages to the proangiogenic M2-type and subsequent neovascularization, The Journal of biological chemistry, doi:10.1074/jbc.m113.535765
Henehan, Montuno, De Benedetto, Doxycycline as an anti-inflammatory agent: updates in dermatology, J Eur Acad Dermatol Venereol, doi:10.1111/jdv.14345
Hu, Chen, Li, Dou, Zhou et al., Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9, Protein Sci, doi:10.1002/pro.3150
Ivanov, Hertzig, Rozanov, Bayer, Thiel et al., Major genetic marker of nidoviruses encodes a replicative endoribonuclease, Proc Natl Acad Sci U S A, doi:10.1073/pnas.0403127101
Kang, Bhardwaj, Li, Palaninathan, Sacchettini et al., Biochemical and genetic analyses of murine hepatitis virus Nsp15 endoribonuclease, J Virol, doi:10.1128/JVI.00547-07
Li, Structure, Function, and Evolution of Coronavirus Spike Proteins, Annu Rev Virol, doi:10.1146/annurev-virology-110615-042301
Lundberg, Pinkham, Baer, Amaya, Narayanan et al., Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication, Antiviral Res, doi:10.1016/j.antiviral.2013.10.004
Maurya, Evaluation of Yashtimadhu (Glycyrrhiza glabra) active Phytochemicals Against Novel Coronavirus (SARS-CoV-2), Research Square, doi:.org/10.21203/rs.21203.rs-26480/v21201+
Maurya, Sharma, Evaluation of Traditional Ayurvedic Preparation for Prevention and Management of the Novel Coronavirus (SARS-CoV-2) Using Molecular Docking Approach, ChemRxiv (Preprints, doi:10.26434/chemrxiv.12110214
Mcbride, Van Zyl, Fielding, The coronavirus nucleocapsid is a multifunctional protein, Viruses, doi:10.3390/v6082991
Mielech, Chen, Mesecar, Baker, Nidovirus papain-like proteases: multifunctional enzymes with protease, deubiquitinating and deISGylating activities, Virus Res, doi:10.1016/j.virusres.2014.01.025
Pettersen, Goddard, Huang, Couch, Greenblatt et al., UCSF Chimera--a visualization system for exploratory research and analysis, J Comput Chem, doi:10.1002/jcc.20084
Phillips, Gallagher, Weiss, Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion, Journal of Virology, doi:10.1128/JVI.01564-16
Posthuma, Nedialkova, Zevenhoven-Dobbe, Blokhuis, Gorbalenya et al., Site-directed mutagenesis of the Nidovirus replicative endoribonuclease NendoU exerts pleiotropic effects on the arterivirus life cycle, J Virol, doi:10.1128/JVI.80.4.1653-1661.2006
Prajapat, Sarma, Shekhar, Avti, Sinha et al., Drug targets for corona virus: A systematic review, Indian journal of pharmacology, doi:10.4103/ijp
Sturtz, Antimurine retroviral effect of doxycycline, Methods Find Exp Clin Pharmacol, doi:10.1358/mf.1998.20.8.487489
Sutton, Fry, Carter, Sainsbury, Walter et al., The nsp9 replicase protein of SARS-coronavirus, structure and functional insights, Structure, doi:10.1016/j.str.2004.01.016
Tay, Fraser, Chan, Moreland, Rathore 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 Res, doi:10.1016/j.antiviral.2013.06.002
Van Aalten, Bywater, Findlay, Hendlich, Hooft et al., PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules, Journal of Computer-Aided Molecular Design, doi:10.1007/BF00355047
Wang, Zhang, Wu, Niu, Song et al., Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2, Cell, doi:10.1016/j.cell.2020.03.045
Wu, Liu, Yang, Zhang, Zhong et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharmaceutica Sinica B, doi:10.1016/j.apsb.2020.02.008
Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral Res, doi:10.1016/j.antiviral.2020.104760
Yang, Chen, Tu, Yen, Yang, Combinatorial Computational Approaches to Identify Tetracycline Derivatives as Flavivirus Inhibitors, PLOS ONE, doi:10.1371/journal.pone.0000428
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Intensive Care Medicine, doi:10.1007/s00134-020-05985-9
Zhou, Hou, Shen, Huang, Martin et al., Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2, Cell Discovery, doi:10.1038/s41421-020-0153-3
Loading..
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. 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   
Submit