Analgesics
Antiandrogens
Antihistamines
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
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2

Eweas et al., Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908
Jan 2021  
  Post
  Facebook
Share
  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 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host cell. It also binds to Mpro and PLpro of SARS-CoV-2; therefore, it might play a role in preventing the post-translational processing of viral polyproteins. The highly efficient binding of ivermectin to the viral N phosphoprotein and nsp14 is suggestive of its role in inhibiting viral replication and assembly.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
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 3CLpro49, 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.
Eweas et al., 25 Jan 2021, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Ahmad F Eweas, Amr A Alhossary, Ahmed S Abdel-Moneim
Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908
SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease with variable severity and fatal consequences. It was first reported in Wuhan and subsequently caused a global pandemic. The viral spike protein binds with the ACE-2 cell surface receptor for entry, while TMPRSS2 triggers its membrane fusion. In addition, RNA dependent RNA polymerase (RdRp), 3 -5 exoribonuclease (nsp14), viral proteases, N, and M proteins are important in different stages of viral replication. Accordingly, they are attractive targets for different antiviral therapeutic agents. Although many antiviral agents have been used in different clinical trials and included in different treatment protocols, the mode of action against SARS-CoV-2 is still not fully understood. Different potential repurposed drugs, including, chloroquine, hydroxychloroquine, ivermectin, remdesivir, and favipiravir, were screened in the present study. Molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases, and nsp14, was performed. Moreover, the binding affinities of the human ACE-2 receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most promising drugs. Our results suggest that both these drugs utilize different mechanisms at the entry and post-entry stages and could be considered potential inhibitors of SARS-CoV-2 replication.
AUTHOR CONTRIBUTIONS ASA-M contributed conception of the study and critically revised the manuscript. AFE conducted the molecular docking and wrote the first draft of the manuscript. AAA performed the molecular dynamics simulation. ASA-M, AFE, and AAA shared analyzing and discussing the results. All authors contributed to manuscript revision, read, and approved the submitted version. SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2020. 592908/full#supplementary-material Supplementary Figure 3 | RMSD and number of Hydrogen bonds. For every receptor, the RMSD and Hydrogen bonds number for each ligand were demonstrated. Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Abdel-Moneim, Abdelwhab, Evidence for SARS-CoV-2 infection of animal hosts, Pathogens, doi:10.3390/pathogens9070529
Abraham, Murtola, Schulz, Páll, Smith et al., GROMACS: high performance molecular simulations through multilevel parallelism from laptops to supercomputers, SoftwareX, doi:10.1016/j.softx.2015.06.001
Baker, Sept, Joseph, Holst, Mccammon, Electrostatics of nanosystems: application to microtubules and the ribosome, Proc. Natl. Acad. Sci. U.S.A, doi:10.1073/pnas.181342398
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of Covid-19-preliminary report, N. Engl. J. Med, doi:10.1056/NEJMoa2007764
Cai, Yang, Liu, Chen, Shu et al., Experimental treatment with favipiravir for COVID-19: an open-label control study, Engineering, doi:10.1016/j.eng.2020.03.007
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Choy, Wong, Kaewpreedee, Sia, Chen et al., Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104786
Deshpande, Tiwari, Nyayanit, Modak, In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2020.173430
Eckerle, Becker, Halpin, Li, Venter et al., Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing, PLoS Pathog, doi:10.1371/journal.ppat.1000896
Fehr, Perlman, Coronaviruses: an overview of their replication and pathogenesis, Methods Mol. Biol, doi:10.1007/978-1-4939-2438-7_1
Gao, Yan, Huang, Liu, Zhao et al., Structure of the RNA-dependent RNA polymerase from COVID-19 virus, Science, doi:10.1126/science.abb7498
Glowacka, Bertram, Müller, Allen, Soilleux et al., Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response, J. Virol, doi:10.1128/JVI.02232-10
Gurung, In silico structure modelling of SARS-CoV-2 Nsp13 helicase and Nsp14 and repurposing of FDA approved antiviral drugs as dual inhibitors, Gene Rep, doi:10.1016/j.genrep.2020.100860
Hall, Ji, A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease, Travel Med. Infect. Dis, doi:10.1016/j.tmaid.2020.101646
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
Hosein, Moore, Known SARS-CoV-2 infections: the tip of an important iceberg, Int. J. Health Plann. Manage, doi:10.1002/hpm.3006
Ivanov, Thiel, Dobbe, Van Der Meer, Snijder et al., Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase, J. Virol, doi:10.1128/JVI.78.11.5619-5632.2004
Kang, Yang, Hong, Zhang, Huang et al., Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites, Acta Pharm. Sin. B, doi:10.1016/j.apsb.2020.04.009
Kumar, Singh, Patel, In silico prediction of potential inhibitors for the main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing, J. Infect. Public Health, doi:10.1016/j.jiph.2020.06.016
Kumari, Kumar, g_mmpbsa-a GROMACS tool for high-throughput MM-PBSA calculations, J. Chem. Inf. Model, doi:10.1021/ci500020m
Kwiek, Haystead, Rudolph, Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines, Biochemistry, doi:10.1021/bi035923w
Lehrer, Rheinstein, Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2, Vivo, doi:10.21873/invivo.12134
Ma, Wu, Shaw, Gao, Wang et al., Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex, Proc. Natl. Acad. Sci. U.S.A, doi:10.1073/pnas.1508686112
Maier, Martinez, Kasavajhala, Wickstrom, Hauser et al., ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB, J. Chem. Theory Comput, doi:10.1021/acs.jctc.5b00255
Mielech, Chen, Mesecar, Baker, Nidovirus papainlike proteases: multifunctional enzymes with protease, deubiquitinating and deISGylating activities, Virus Res, doi:10.1016/j.virusres.2014.01.025
Mugisha, Vuong, Puray-Chavez, Kutluay, A facile Q-RT-PCR assay for monitoring SARS-CoV-2 growth in cell culture, bioRxiv, doi:10.1101/2020.06.26.174698
Osipiuk, Jedrzejczak, Tesar, Endres, Stols et al., The crystal structure of papain-like protease of SARS CoV-2, Center for Structural Genomics of Infectious Diseases, doi:10.2210/pdb6w9c/pdb
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
Rowland, Chauhan, Fang, Pekosz, Kerrigan et al., Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells, J. Virol, doi:10.1128/JVI.79.17.11507-11512.2005
Sali, Blundell, Comparative protein modelling by satisfaction of spatial restraints, J. Mol. Biol, doi:10.1006/jmbi.1993.1626
Savarino, Di Trani, Donatelli, Cauda, Cassone, New insights into the antiviral effects of chloroquine, Lancet Infect. Dis, doi:10.1016/S1473-3099(06)70361-9
Shannon, Selisko, Le, Huchting, Touret et al., Favipiravir strikes the SARS-CoV-2 at its achilles heel, the RNA polymerase, doi:10.1101/2020.05.15.098731
Sheahan, Sims, Leist, Schäfer, Won et al., Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV, Nat. Commun, doi:10.1038/s41467-019-13940-6
Siu, Teoh, Lo, Chan, Kien et al., The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles, J. Virol, doi:10.1128/JVI.01052-08
Sousa Da Silva, Vranken, ACPYPE -AnteChamber PYthon Parser interfacE, BMC Res. Notes, doi:10.1186/1756-0500-5-367
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
Timani, Liao, Ye, Zeng, Liu et al., Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus, Virus Res, doi:10.1016/j.virusres.2005.05.007
Vincent, Bergeron, Benjannet, Erickson, Rollin et al., Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol. J, doi:10.1186/1743-422X-2-69
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J, doi:10.1042/BJ20120150
Walls, Park, Tortorici, Wall, Mcguire et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Cell, doi:10.1016/j.cell.2020.11.032
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Wang, Wang, Kollman, Case, Automatic atom type and bond type perception in molecular mechanical calculations, J. Mol. Graph. Model, doi:10.1016/j.jmgm.2005.12.005
Wang, Zhang, Du, Du, Zhao et al., Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet
Warren, Jordan, Lo, Ray, Mackman et al., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys, Nature
Wu, Liu, Yang, Zhang, Zhong et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharm. Sin. B
Wu, Peng, Huang, Ding, Wang et al., Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China, Cell Host Microbe
Xu, Liu, Weiss, Arnold, Sarafianos et al., Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design, Nucleic Acids Res
Yan, Zou, Sun, Li, Xu et al., Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model, Cell Res
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
Yin, Mao, Luan, Shen, Shen et al., Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir, Science, doi:10.1126/science.abc1560
Zhang, Lin, Sun, Curth, Drosten et al., Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science, doi:10.1126/science.abb3405
Zhao, Jha, Wu, Elliott, Ziebuhr et al., Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology, Cell Host Microbe, doi:10.1016/j.chom.2012.04.011
Zhu, Zhang, Wang, Li, Yang et al., A novel coronavirus from patients with pneumonia in China, N. Engl. J. Med, doi:10.1056/NEJMoa2001017
Ziebuhr, Snijder, Gorbalenya, Virus-encoded proteinases and proteolytic processing in the Nidovirales, J. Gen. Virol, doi:10.1099/0022-1317-81-4-853
{ 'indexed': {'date-parts': [[2024, 4, 2]], 'date-time': '2024-04-02T10:54:47Z', 'timestamp': 1712055287979}, 'reference-count': 57, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2021, 1, 25]], 'date-time': '2021-01-25T00:00:00Z', 'timestamp': 1611532800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'DOI': '10.13039/501100006261', 'name': 'Taif University', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:p>SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease with ' 'variable severity and fatal consequences. It was first reported in Wuhan and subsequently ' 'caused a global pandemic. The viral spike protein binds with the ACE-2 cell surface receptor ' 'for entry, while TMPRSS2 triggers its membrane fusion. In addition, RNA dependent RNA ' 'polymerase (RdRp), 3′–5′ exoribonuclease (nsp14), viral proteases, N, and M proteins are ' 'important in different stages of viral replication. Accordingly, they are attractive targets ' 'for different antiviral therapeutic agents. Although many antiviral agents have been used in ' 'different clinical trials and included in different treatment protocols, the mode of action ' 'against SARS-CoV-2 is still not fully understood. Different potential repurposed drugs, ' 'including, chloroquine, hydroxychloroquine, ivermectin, remdesivir, and favipiravir, were ' 'screened in the present study. Molecular docking of these drugs with different SARS-CoV-2 ' 'target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral ' 'proteases, and nsp14, was performed. Moreover, the binding affinities of the human ACE-2 ' 'receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and ' 'MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most ' 'promising drugs. Our results suggest that both these drugs utilize different mechanisms at ' 'the entry and post-entry stages and could be considered potential inhibitors of SARS-CoV-2 ' 'replication.</jats:p>', 'DOI': '10.3389/fmicb.2020.592908', 'type': 'journal-article', 'created': {'date-parts': [[2021, 1, 25]], 'date-time': '2021-01-25T05:25:07Z', 'timestamp': 1611552307000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 62, 'title': 'Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against ' 'SARS-CoV-2', 'prefix': '10.3389', 'volume': '11', 'author': [ {'given': 'Ahmad F.', 'family': 'Eweas', 'sequence': 'first', 'affiliation': []}, {'given': 'Amr A.', 'family': 'Alhossary', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ahmed S.', 'family': 'Abdel-Moneim', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2021, 1, 25]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/pathogens9070529', 'article-title': 'Evidence for SARS-CoV-2 infection of animal hosts.', 'volume': '9', 'author': 'Abdel-Moneim', 'year': '2020', 'journal-title': 'Pathogens'}, { 'key': 'B2', 'doi-asserted-by': 'publisher', 'first-page': '19', 'DOI': '10.1016/j.softx.2015.06.001', 'article-title': 'GROMACS: high performance molecular simulations through multi-level ' 'parallelism from laptops to supercomputers.', 'volume': '1', 'author': 'Abraham', 'year': '2015', 'journal-title': 'SoftwareX'}, { 'key': 'B3', 'doi-asserted-by': 'publisher', 'first-page': '10037', 'DOI': '10.1073/pnas.181342398', 'article-title': 'Electrostatics of nanosystems: application to microtubules and the ' 'ribosome.', 'volume': '98', 'author': 'Baker', 'year': '2001', 'journal-title': 'Proc. Natl. Acad. Sci. U.S.A.'}, { 'key': 'B4', 'doi-asserted-by': 'publisher', 'first-page': '1813', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the treatment of Covid-19—preliminary report.', 'volume': '383', 'author': 'Beigel', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B5', 'doi-asserted-by': 'publisher', 'first-page': '1192', 'DOI': '10.1016/j.eng.2020.03.007', 'article-title': 'Experimental treatment with favipiravir for COVID-19: an open-label ' 'control study.', 'volume': '6', 'author': 'Cai', 'year': '2020', 'journal-title': 'Engineering'}, { 'key': 'B6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2020.104787', 'article-title': 'The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 ' 'in vitro.', 'volume': '178', 'author': 'Caly', 'year': '2020', 'journal-title': 'Antiviral Res.'}, { 'key': 'B7', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2020.104786', 'article-title': 'Remdesivir, lopinavir, emetine, and homoharringtonine inhibit ' 'SARS-CoV-2 replication in vitro.', 'volume': '178', 'author': 'Choy', 'year': '2020', 'journal-title': 'Antiviral Res.'}, { 'key': 'B8', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ejphar.2020.173430', 'article-title': 'In silico molecular docking analysis for repurposing therapeutics ' 'against multiple proteins from SARS-CoV-2.', 'volume': '886', 'author': 'Deshpande', 'year': '2020', 'journal-title': 'Eur. J. Pharmacol.'}, { 'key': 'B9', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.ppat.1000896', 'article-title': 'Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is ' 'revealed by complete genome sequencing.', 'volume': '6', 'author': 'Eckerle', 'year': '2010', 'journal-title': 'PLoS Pathog.'}, { 'key': 'B10', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1007/978-1-4939-2438-7_1', 'article-title': 'Coronaviruses: an overview of their replication and pathogenesis.', 'volume': '1282', 'author': 'Fehr', 'year': '2015', 'journal-title': 'Methods Mol. Biol.'}, { 'key': 'B11', 'doi-asserted-by': 'publisher', 'first-page': '779', 'DOI': '10.1126/science.abb7498', 'article-title': 'Structure of the RNA-dependent RNA polymerase from COVID-19 virus.', 'volume': '368', 'author': 'Gao', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'B12', 'doi-asserted-by': 'publisher', 'first-page': '4122', 'DOI': '10.1128/JVI.02232-10', 'article-title': 'Evidence that TMPRSS2 activates the severe acute respiratory syndrome ' 'coronavirus spike protein for membrane fusion and reduces viral control ' 'by the humoral immune response.', 'volume': '85', 'author': 'Glowacka', 'year': '2011', 'journal-title': 'J. Virol.'}, { 'key': 'B13', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.genrep.2020.100860', 'article-title': 'In silico structure modelling of SARS-CoV-2 Nsp13 helicase and Nsp14 ' 'and repurposing of FDA approved antiviral drugs as dual inhibitors.', 'volume': '21', 'author': 'Gurung', 'year': '2020', 'journal-title': 'Gene Rep.'}, { 'key': 'B14', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2020.101646', 'article-title': 'A search for medications to treat COVID-19 via in silico molecular ' 'docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease.', 'volume': '35', 'author': 'Hall', 'year': '2020', 'journal-title': 'Travel Med. Infect. Dis.'}, { 'key': 'B15', 'doi-asserted-by': 'publisher', 'first-page': '271.e8', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a ' 'clinically proven protease inhibitor.', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'B16', 'doi-asserted-by': 'publisher', 'first-page': '1270', 'DOI': '10.1002/hpm.3006', 'article-title': 'Known SARS-CoV-2 infections: the tip of an important iceberg.', 'volume': '35', 'author': 'Hosein', 'year': '2020', 'journal-title': 'Int. J. Health Plann. Manage.'}, { 'key': 'B17', 'doi-asserted-by': 'publisher', 'first-page': '5619', 'DOI': '10.1128/JVI.78.11.5619-5632.2004', 'article-title': 'Multiple enzymatic activities associated with severe acute respiratory ' 'syndrome coronavirus helicase.', 'volume': '78', 'author': 'Ivanov', 'year': '2004', 'journal-title': 'J. Virol.'}, { 'key': 'B18', 'doi-asserted-by': 'publisher', 'first-page': '1228', 'DOI': '10.1016/j.apsb.2020.04.009', 'article-title': 'Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain ' 'reveals potential unique drug targeting sites.', 'volume': '10', 'author': 'Kang', 'year': '2020', 'journal-title': 'Acta Pharm. Sin. B'}, { 'key': 'B19', 'doi-asserted-by': 'publisher', 'first-page': '1210', 'DOI': '10.1016/j.jiph.2020.06.016', 'article-title': 'In silico prediction of potential inhibitors for the main protease of ' 'SARS-CoV-2 using molecular docking and dynamics simulation based ' 'drug-repurposing.', 'volume': '13', 'author': 'Kumar', 'year': '2020', 'journal-title': 'J. Infect. Public Health'}, { 'key': 'B20', 'doi-asserted-by': 'publisher', 'first-page': '1951', 'DOI': '10.1021/ci500020m', 'article-title': 'g_mmpbsa–a GROMACS tool for high-throughput MM-PBSA calculations.', 'volume': '54', 'author': 'Kumari', 'year': '2014', 'journal-title': 'J. Chem. Inf. Model'}, { 'key': 'B21', 'doi-asserted-by': 'publisher', 'first-page': '4538', 'DOI': '10.1021/bi035923w', 'article-title': 'Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the ' 'antimalarial quinolines.', 'volume': '43', 'author': 'Kwiek', 'year': '2004', 'journal-title': 'Biochemistry'}, { 'key': 'B22', 'doi-asserted-by': 'publisher', 'first-page': '3023', 'DOI': '10.21873/invivo.12134', 'article-title': 'Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain ' 'attached to ACE2.', 'volume': '34', 'author': 'Lehrer', 'year': '2020', 'journal-title': 'In Vivo'}, { 'key': 'B23', 'doi-asserted-by': 'publisher', 'first-page': '9436', 'DOI': '10.1073/pnas.1508686112', 'article-title': 'Structural basis and functional analysis of the SARS coronavirus ' 'nsp14-nsp10 complex.', 'volume': '112', 'author': 'Ma', 'year': '2015', 'journal-title': 'Proc. Natl. Acad. Sci. U.S.A.'}, { 'key': 'B24', 'doi-asserted-by': 'publisher', 'first-page': '3696', 'DOI': '10.1021/acs.jctc.5b00255', 'article-title': 'ff14SB: improving the accuracy of protein side chain and backbone ' 'parameters from ff99SB.', 'volume': '11', 'author': 'Maier', 'year': '2015', 'journal-title': 'J. Chem. Theory Comput.'}, { 'key': 'B25', 'doi-asserted-by': 'publisher', 'first-page': '184', 'DOI': '10.1016/j.virusres.2014.01.025', 'article-title': 'Nidovirus papain-like proteases: multifunctional enzymes with protease, ' 'deubiquitinating and deISGylating activities.', 'volume': '194', 'author': 'Mielech', 'year': '2014', 'journal-title': 'Virus Res.'}, { 'key': 'B26', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.06.26.174698', 'article-title': 'A facile Q-RT-PCR assay for monitoring SARS-CoV-2 growth in cell ' 'culture.', 'author': 'Mugisha', 'year': '2020', 'journal-title': 'bioRxiv [Prepint]'}, { 'key': 'B27', 'year': '2020', 'journal-title': 'First Antiviral Drug Approved to Fight Coronavirus. 2020.'}, { 'key': 'B28', 'doi-asserted-by': 'publisher', 'DOI': '10.2210/pdb6w9c/pdb', 'article-title': '“The crystal structure of papain-like protease of SARS CoV-2,”', 'author': 'Osipiuk', 'year': '2020', 'journal-title': 'Center for Structural Genomics of Infectious Diseases (CSGID)'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'first-page': '1605', 'DOI': '10.1002/jcc.20084', 'article-title': 'UCSF chimera–a visualization system for exploratory research and ' 'analysis.', 'volume': '25', 'author': 'Pettersen', 'year': '2004', 'journal-title': 'J. Comput. Chem.'}, { 'key': 'B30', 'doi-asserted-by': 'publisher', 'first-page': '11507', 'DOI': '10.1128/JVI.79.17.11507-11512.2005', 'article-title': 'Intracellular localization of the severe acute respiratory syndrome ' 'coronavirus nucleocapsid protein: absence of nucleolar accumulation ' 'during infection and after expression as a recombinant protein in vero ' 'cells.', 'volume': '79', 'author': 'Rowland', 'year': '2005', 'journal-title': 'J. Virol.'}, { 'key': 'B31', 'doi-asserted-by': 'publisher', 'first-page': '779', 'DOI': '10.1006/jmbi.1993.1626', 'article-title': 'Comparative protein modelling by satisfaction of spatial restraints.', 'volume': '234', 'author': 'Sali', 'year': '1993', 'journal-title': 'J. Mol. Biol.'}, { 'key': 'B32', 'doi-asserted-by': 'publisher', 'first-page': '67', 'DOI': '10.1016/S1473-3099(06)70361-9', 'article-title': 'New insights into the antiviral effects of chloroquine.', 'volume': '6', 'author': 'Savarino', 'year': '2006', 'journal-title': 'Lancet Infect. Dis.'}, { 'key': 'B33', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.05.15.098731', 'article-title': 'Favipiravir strikes the SARS-CoV-2 at its achilles heel, the RNA ' 'polymerase.', 'author': 'Shannon', 'year': '2020', 'journal-title': 'bioRxiv [Preprint]'}, { 'key': 'B34', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41467-019-13940-6', 'article-title': 'Comparative therapeutic efficacy of remdesivir and combination ' 'lopinavir, ritonavir, and interferon beta against MERS-CoV.', 'volume': '11', 'author': 'Sheahan', 'year': '2020', 'journal-title': 'Nat. Commun.'}, { 'key': 'B35', 'doi-asserted-by': 'publisher', 'first-page': '11318', 'DOI': '10.1128/JVI.01052-08', 'article-title': 'The M, E, and N structural proteins of the severe acute respiratory ' 'syndrome coronavirus are required for efficient assembly, trafficking, ' 'and release of virus-like particles.', 'volume': '82', 'author': 'Siu', 'year': '2008', 'journal-title': 'J. Virol.'}, { 'key': 'B36', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1756-0500-5-367', 'article-title': 'ACPYPE - AnteChamber PYthon Parser interfacE.', 'volume': '5', 'author': 'Sousa da Silva', 'year': '2012', 'journal-title': 'BMC Res. Notes'}, { 'key': 'B37', 'doi-asserted-by': 'publisher', 'first-page': '301', 'DOI': '10.1016/j.antiviral.2013.06.002', 'article-title': 'Nuclear localization of dengue virus (DENV) 1–4 non-structural protein ' '5; protection against all 4 DENV serotypes by the inhibitor Ivermectin.', 'volume': '99', 'author': 'Tay', 'year': '2013', 'journal-title': 'Antiviral Res.'}, { 'key': 'B38', 'doi-asserted-by': 'publisher', 'first-page': '23', 'DOI': '10.1016/j.virusres.2005.05.007', 'article-title': 'Nuclear/nucleolar localization properties of C-terminal nucleocapsid ' 'protein of SARS coronavirus.', 'volume': '114', 'author': 'Timani', 'year': '2005', 'journal-title': 'Virus Res.'}, { 'key': 'B39', 'doi-asserted-by': 'publisher', 'first-page': 'D506', 'DOI': '10.1093/nar/gky1049', 'article-title': 'UniProt: a worldwide hub of protein knowledge.', 'volume': '47', 'year': '2019', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'B40', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1743-422X-2-69', 'article-title': 'Chloroquine is a potent inhibitor of SARS coronavirus infection and ' 'spread.', 'volume': '2', 'author': 'Vincent', 'year': '2005', 'journal-title': 'Virol. J.'}, { 'key': 'B41', 'doi-asserted-by': 'publisher', 'first-page': '851', 'DOI': '10.1042/BJ20120150', 'article-title': 'Ivermectin is a specific inhibitor of importin α/β-mediated nuclear ' 'import able to inhibit replication of HIV-1 and dengue virus.', 'volume': '443', 'author': 'Wagstaff', 'year': '2012', 'journal-title': 'Biochem. J.'}, { 'key': 'B42', 'doi-asserted-by': 'publisher', 'first-page': '281.e6', 'DOI': '10.1016/j.cell.2020.11.032', 'article-title': 'Structure, function, and antigenicity of the SARS-CoV-2 spike ' 'glycoprotein.', 'volume': '181', 'author': 'Walls', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'B43', 'doi-asserted-by': 'publisher', 'first-page': '247', 'DOI': '10.1016/j.jmgm.2005.12.005', 'article-title': 'Automatic atom type and bond type perception in molecular mechanical ' 'calculations.', 'volume': '25', 'author': 'Wang', 'year': '2006', 'journal-title': 'J. Mol. Graph. Model'}, { 'key': 'B44', 'doi-asserted-by': 'publisher', 'first-page': '269', 'DOI': '10.1038/s41422-020-0282-0', 'article-title': 'Remdesivir and chloroquine effectively inhibit the recently emerged ' 'novel coronavirus (2019-nCoV) in vitro.', 'volume': '30', 'author': 'Wang', 'year': '2020', 'journal-title': 'Cell Res.'}, { 'key': 'B45', 'doi-asserted-by': 'crossref', 'first-page': '1569', 'DOI': '10.1016/S0140-6736(20)31022-9', 'article-title': 'Remdesivir in adults with severe COVID-19: a randomised, double-blind, ' 'placebo-controlled, multicentre trial.', 'volume': '395', 'author': 'Wang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'B46', 'doi-asserted-by': 'crossref', 'first-page': '381', 'DOI': '10.1038/nature17180', 'article-title': 'Therapeutic efficacy of the small molecule GS-5734 against Ebola virus ' 'in rhesus monkeys.', 'volume': '531', 'author': 'Warren', 'year': '2016', 'journal-title': 'Nature'}, { 'key': 'B47', 'year': '2020', 'journal-title': 'WHO Coronavirus Disease (COVID-19) Dashboard.'}, { 'key': 'B48', 'doi-asserted-by': 'crossref', 'first-page': '325', 'DOI': '10.1016/j.chom.2020.02.001', 'article-title': 'Genome composition and divergence of the novel coronavirus (2019-nCoV) ' 'originating in China.', 'volume': '27', 'author': 'Wu', 'year': '2020', 'journal-title': 'Cell Host Microbe'}, { 'key': 'B49', 'doi-asserted-by': 'crossref', 'first-page': '766', 'DOI': '10.1016/j.apsb.2020.02.008', 'article-title': 'Analysis of therapeutic targets for SARS-CoV-2 and discovery of ' 'potential drugs by computational methods.', 'volume': '10', 'author': 'Wu', 'year': '2020', 'journal-title': 'Acta Pharm. Sin. B'}, { 'key': 'B50', 'doi-asserted-by': 'crossref', 'first-page': '7117', 'DOI': '10.1093/nar/gkg916', 'article-title': 'Molecular model of SARS coronavirus polymerase: implications for ' 'biochemical functions and drug design.', 'volume': '31', 'author': 'Xu', 'year': '2003', 'journal-title': 'Nucleic Acids Res.'}, { 'key': 'B51', 'doi-asserted-by': 'crossref', 'first-page': '300', 'DOI': '10.1038/cr.2012.165', 'article-title': 'Anti-malaria drug chloroquine is highly effective in treating avian ' 'influenza A H5N1 virus infection in an animal model.', 'volume': '23', 'author': 'Yan', 'year': '2013', 'journal-title': 'Cell Res.'}, { 'key': 'B52', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2020.104760', 'article-title': 'The broad spectrum antiviral ivermectin targets the host nuclear ' 'transport importin α/β1 heterodimer.', 'volume': '177', 'author': 'Yang', 'year': '2020', 'journal-title': 'Antiviral Res.'}, { 'key': 'B53', 'doi-asserted-by': 'publisher', 'first-page': '1499', 'DOI': '10.1126/science.abc1560', 'article-title': 'Structural basis for inhibition of the RNA-dependent RNA polymerase ' 'from SARS-CoV-2 by remdesivir.', 'volume': '368', 'author': 'Yin', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'B54', 'doi-asserted-by': 'publisher', 'first-page': '409', 'DOI': '10.1126/science.abb3405', 'article-title': 'Crystal structure of SARS-CoV-2 main protease provides a basis for ' 'design of improved α-ketoamide inhibitors.', 'volume': '368', 'author': 'Zhang', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'B55', 'doi-asserted-by': 'publisher', 'first-page': '607', 'DOI': '10.1016/j.chom.2012.04.011', 'article-title': 'Antagonism of the interferon-induced OAS-RNase L pathway by murine ' 'coronavirus ns2 protein is required for virus replication and liver ' 'pathology.', 'volume': '11', 'author': 'Zhao', 'year': '2012', 'journal-title': 'Cell Host Microbe'}, { 'key': 'B56', 'doi-asserted-by': 'publisher', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'article-title': 'A novel coronavirus from patients with pneumonia in China, 2019.', 'volume': '382', 'author': 'Zhu', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B57', 'doi-asserted-by': 'publisher', 'first-page': '853', 'DOI': '10.1099/0022-1317-81-4-853', 'article-title': 'Virus-encoded proteinases and proteolytic processing in the ' 'Nidovirales.', 'volume': '81', 'author': 'Ziebuhr', 'year': '2000', 'journal-title': 'J. Gen. Virol.'}], 'container-title': 'Frontiers in Microbiology', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fmicb.2020.592908/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 2, 22]], 'date-time': '2021-02-22T17:09:48Z', 'timestamp': 1614013788000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fmicb.2020.592908/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 1, 25]]}, 'references-count': 57, 'alternative-id': ['10.3389/fmicb.2020.592908'], 'URL': 'http://dx.doi.org/10.3389/fmicb.2020.592908', 'relation': {}, 'ISSN': ['1664-302X'], 'subject': [], 'container-title-short': 'Front. Microbiol.', 'published': {'date-parts': [[2021, 1, 25]]}}
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. 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.
  or use drag and drop   
Submit