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
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
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 PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis       

Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities

Wehbe et al., Front. Immunol., doi:10.3389/fimmu.2021.663586
Mar 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 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19ivm.org
Review of how ivermectin was identified for use in COVID-19, mechanisms of action, and selected clinical trials.
Reviews covering ivermectin for COVID-19 include1-45.
Wehbe et al., 30 Mar 2021, peer-reviewed, 7 authors.
This PaperIvermectinAll
Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities
Zena Wehbe, Maya Wehbe, Rabah Iratni, Gianfranco Pintus, Hassan Zaraket, Hadi M Yassine, Ali H Eid
Frontiers in Immunology, doi:10.3389/fimmu.2021.663586
As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action-and finally, we culminate with the current clinical findings.
AUTHOR CONTRIBUTIONS AE generated the concept. ZW and MW wrote the first draft. All authors revised the manuscript and approved it before submission. HY generated funding. 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
Agostini, Andres, Sims, Graham, Sheahan et al., Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease, mBio, doi:10.1128/mBio.00221-18
Ahmed, Karim, Ross, Hossain, Clemens et al., A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness, Int J Infect Dis, doi:10.1016/j.ijid.2020.11.191
Alexander, Bockarie, Kastens, Kazura, Alpers, Absence of ivermectin-associated excess deaths, Trans R Soc Trop Med Hyg, doi:10.1016/s0035-9203(98)91035-5
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the Treatment of Covid-19 -Final Report, N Engl J Med, doi:10.1056/NEJMoa2007764
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
Camprubı́d, Martı-Soler, Soriano, Hurtado, Subirà, Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients, PloS One, doi:10.1371/journal.pone.0242184
Chaccour, Ruiz-Castillo, Richardson, Moncunill, Casellas et al., The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission in low risk, non-severe COVID-19 patients in the first 48 hours after symptoms onset: A structured summary of a study protocol for a randomized control pilot trial, Trials, doi:10.1186/s13063-020-04421-z
Chen, Nirula, Heller, Gottlieb, Boscia et al., SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2029849
Chen, Wang, Wang, Wei, Mutations Strengthened SARS-CoV-2 Infectivity, J Mol Biol, doi:10.1016/j.jmb.2020.07.009
Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet, doi:10.1016/S0140-6736(20)30211-7
Cokol, Nair, Rost, Finding nuclear localization signals, EMBO Rep, doi:10.1093/embo-reports/kvd092
Cong, Ulasli, Schepers, Mauthe, V'kovski et al., Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle, J Virol, doi:10.1128/JVI.01925-19
Crump, Ivermectin, 'wonder drug' from Japan: the human use perspective, Proc Jpn Acad Ser B Phys Biol Sci, doi:10.2183/pjab.87.13
De Melo, Lazarini, Larrous, Feige, Kergoat et al., Anti-COVD-19 efficacy of ivermectin in the golden hamster, BioRxiv, doi:10.1101/2020.11.21.392639
Fried, Kutay, Nucleocytoplasmic transport: taking an inventory, Cell Mol Life Sci, doi:10.1007/s00018-003-3070-3
Fulcher, Jans, Regulation of nucleocytoplasmic trafficking of viral proteins: an integral role in pathogenesis?, Biochim Biophys Acta, doi:10.1016/j.bbamcr.2011.03.019
Goldfarb, Corbett, Mason, Harreman, Adam, Importin alpha: a multipurpose nuclear-transport receptor, Trends Cell Biol, doi:10.1016/j.tcb.2004.07.016
Gordon, Mouncey, Al-Beidh, Rowan, Nichol et al., Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 -Preliminary report, N Engl J Med, doi:10.1056/NEJMoa2100433
Gotz, Magar, Dornfeld, Giese, Pohlmann et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Sci Rep, doi:10.1038/srep23138
Gupta, Biswal, Panda, Ray, Rana, Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-a with, J Biomol Struct Dyn, doi:10.1080/07391102.2020.1839564
Gussow, Auslander, Faure, Wolf, Zhang et al., Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses, Proc Natl Acad Sci, doi:10.1073/pnas.2008176117
Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, J Clin Pharmacol, doi:10.1177/009127002401382731
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
Horby, Lim, Emberson, Mafham, Bell et al., Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report, N Engl J Med, doi:10.1056/NEJMoa2021436
Hu, Sneyd, Dekant, Wang, Influenza A Virus Nucleoprotein: A Highly Conserved Multi-Functional Viral Protein as a Hot Antiviral Drug Target, Curr Top M ed Chem, doi:10.2174/1568026617666170224122508
Hurst, Koetzner, Masters, Characterization of a critical interaction between the coronavirus nucleocapsid protein and nonstructural protein 3 of the viral replicase-transcriptase complex, J Virol, doi:10.1128/JVI.01275-13
Ikeda, Canga, Prieto, Liebana, Martıńez et al., Pharmacological effects of ivermectin, an antiparasitic agent for intestinal strongyloidiasis: its mode of action and clinical efficacy, Nihon Yakurigaku Zasshi, doi:10.1208/s12248-007-9000-9
Jeffreys, Pennington, Duggan, Breen, Jinks et al., Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2, doi:10.1101/2020.12.23.424232
Juarez, Schcolnik-Cabrera, Dueñas-Gonzalez, The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug, Am J Cancer Res
Kaddoura, Alibrahim, Hijazi, Soudani, Alkalamouni, COVID-19 Therapeutic Options Under Investigation, Front Pharmacol, doi:10.3389/fphar.2020.01196
Kaur, Shekhar, Sharma, Sarma, Prakash et al., Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes, Pharmacol Rep, doi:10.1007/s43440-020-00195-y
Kosyna, Nagel, Kluxen, Kraushaar, Depping, The importin a/ b-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biol Chem, doi:10.1515/hsz-2015-0171
Larder, Viral resistance and the selection of antiretroviral combinations, J Acquir Immune Defic Syndr Hum Retrovirol, doi:10.1097/00042560-199510001-00007
Lin, Lin, Hsu, Chang, Chien et al., Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design, J Med Chem, doi:10.1021/acs.jmedchem.9b01913
Lu, Wang, Gao, Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV, MERS-CoV, and beyond, Trends Microbiol, doi:10.1016/j.tim.2015.06.003
Mathew, Faheem, Hassain, Benslimane, Thani et al., Platforms Exploited for SARS-CoV-2 Vaccine Development, Vaccines, doi:10.3390/vaccines9010011
Mcbride, Van Zyl, Fielding, The coronavirus nucleocapsid is a multifunctional protein, Viruses, doi:10.3390/v6082991
Moriyama, Nagai, Oka, Ikawa, Okabe et al., Targeted disruption of one of the importin a family members leads to female functional incompetence in delivery, FEBS J, doi:10.1111/j.1742-4658.2011.08079.x
Njoo, Hack, Oosting, Luyendijk, Stilma et al., C-reactive protein and interleukin-6 are elevated in onchocerciasis patients after ivermectin treatment, J Infect Dis, doi:10.1093/infdis/170.3.663
Oka, Yoneda, Importin a: functions as a nuclear transport factor and beyond, Proc Jpn Acad Ser B Phys Biol Sci, doi:10.2183/pjab.94.018
Pan, Peto, Henao-Restrepo, Preziosi, Sathiyamoorthy et al., Repurposed Antiviral Drugs for Covid-19 -Interim WHO Solidarity Trial Results, N Engl J Med, doi:10.1056/NEJMoa2023184
Rajter, Sherman, Fatteh, Vogel, Sacks et al., Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study, Chest, doi:10.1016/j.chest.2020.10.009
Romano, Ruggiero, Squeglia, Maga, Berisio, A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping, Cells, doi:10.3390/cells9051267
Rout, Aitchison, Pore relations: nuclear pore complexes and nucleocytoplasmic exchange, Essays Biochem, doi:10.1042/bse0360075
Santos, Grosche, Bergamini, Sabino-Silva, Jardim, Antivirals Against Coronaviruses: Candidate Drugs for SARS-CoV-2 Treatment?, Front Microbiol, doi:10.3389/fmicb.2020.01818
Savastano, De Opakua, Rankovic, Zweckstetter, Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates, Nat Commun, doi:10.1038/s41467-020-19843-1
Sawicki, Sawicki, A new model for coronavirus transcription, Adv Exp Med Biol, doi:10.1007/978-1-4615-5331-1_26
Schröder, Swan, Soll, Hotson, Efficacy of ivermectin against ectoparasites of cattle in South Africa, J S Afr Vet Assoc
Seward, Reactions in dogs given ivermectin, J Am Vet Med Assoc
Singh, Kulsum, Rufai, Mudliar, Singh, Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development, J Lab Physicians, doi:10.1055/s-0040-1715790
Tablets, STROMECTOL ® (IVERMECTIN
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
Wagstaff, Rawlinson, Hearps, Jans, An AlphaScreen ® -based assay for high-throughput screening for specific inhibitors of nuclear import, J Biomol Screen, doi:10.1177/1087057110390360
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin a/b-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem J, doi:10.1042/BJ20120150
Wang, Grunewald, Perlman, Coronaviruses: An Updated Overview of Their Replication and Pathogenesis, Methods Mol Biol, doi:10.1007/978-1-0716-0900-2_1
Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a Neutralizing Antibody CocktailOutpatients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2035002
Weis, Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle, Cell, doi:10.1016/s0092-8674(03)00082-5
Wurm, Chen, Hodgson, Britton, Brooks et al., Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division, J Virol, doi:10.1128/JVI.75.19.9345-9356.2001
Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin a/b1 heterodimer, Antiviral Res, doi:10.1016/j.antiviral.2020.104760
You, Reed, Hiscox, Trafficking motifs in the SARS-coronavirus nucleocapsid protein, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2007.05.036
Zeng, Liu, Ma, Zhao, Yang et al., Biochemical characterization of SARS-CoV-2 nucleocapsid protein, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2020.04.136
Zhang, Song, Ci, Ju, Li, Ivermectin inhibits LPSinduced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflamm Res, doi:10.1007/s00011-008-8007-8
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, 17]], 'date-time': '2024-04-17T11:59:40Z', 'timestamp': 1713355180707}, 'reference-count': 65, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2021, 3, 30]], 'date-time': '2021-03-30T00:00:00Z', 'timestamp': 1617062400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'DOI': '10.13039/501100004252', 'name': 'Qatar University', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:p>As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the ' 'world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of ' 'COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, ' 'have been approved for emergency use in various countries. However, the slow roll-out of ' 'vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. ' 'Moreover, vaccines are important tools for preventing the disease but therapeutic tools to ' 'treat patients are also needed. As such, since the beginning of the pandemic, repurposed ' 'FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to ' 'their known safety profiles and potential anti-viral effects. One of these drugs is ' 'ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral ' 'activity against various viruses including SARS-CoV-2. In this review, we delineate the story ' 'of how this antiparasitic drug was eventually identified as a potential treatment option for ' 'COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning ' 'points in past research that provided initial ‘hints’ for IVM’s antiviral activity and its ' 'molecular mechanism of action- and finally, we culminate with the current clinical ' 'findings.</jats:p>', 'DOI': '10.3389/fimmu.2021.663586', 'type': 'journal-article', 'created': {'date-parts': [[2021, 3, 30]], 'date-time': '2021-03-30T13:12:05Z', 'timestamp': 1617109925000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 23, 'title': 'Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities', 'prefix': '10.3389', 'volume': '12', 'author': [ {'given': 'Zena', 'family': 'Wehbe', 'sequence': 'first', 'affiliation': []}, {'given': 'Maya', 'family': 'Wehbe', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rabah', 'family': 'Iratni', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gianfranco', 'family': 'Pintus', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hassan', 'family': 'Zaraket', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hadi M.', 'family': 'Yassine', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ali H.', 'family': 'Eid', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2021, 3, 30]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1007/978-1-0716-0900-2_1', 'article-title': 'Coronaviruses: An Updated Overview of Their Replication and ' 'Pathogenesis', 'volume': '2203', 'author': 'Wang', 'year': '2020', 'journal-title': 'Methods Mol Biol'}, { 'key': 'B2', 'doi-asserted-by': 'publisher', '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': '2', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'B3', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tim.2015.06.003', 'article-title': 'Bat-to-human: spike features determining ‘host jump’ of coronaviruses ' 'SARS-CoV, MERS-CoV, and beyond', 'volume': '23', 'author': 'Lu', 'year': '2015', 'journal-title': 'Trends Microbiol'}, { 'key': 'B4', 'doi-asserted-by': 'publisher', 'first-page': '11', 'DOI': '10.3390/vaccines9010011', 'article-title': 'Platforms Exploited for SARS-CoV-2 Vaccine Development', 'volume': '9', 'author': 'Mathew', 'year': '2020', 'journal-title': 'Vaccines (Basel)'}, { 'key': 'B5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30211-7', 'article-title': 'Epidemiological and clinical characteristics of 99 cases of 2019 novel ' 'coronavirus pneumonia in Wuhan, China: a descriptive study', 'volume': '395', 'author': 'Chen', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'B6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jmb.2020.07.009', 'article-title': 'Mutations Strengthened SARS-CoV-2 Infectivity', 'volume': '432', 'author': 'Chen', 'year': '2020', 'journal-title': 'J Mol Biol'}, { 'key': 'B7', 'doi-asserted-by': 'publisher', 'DOI': '10.1055/s-0040-1715790', 'article-title': 'Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike ' 'Protein: A Challenge in Vaccine Development', 'volume': '12', 'author': 'Singh', 'year': '2020', 'journal-title': 'J Lab Physicians'}, { 'key': 'B8', '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': 'B9', 'doi-asserted-by': 'publisher', 'first-page': '13', 'DOI': '10.2183/pjab.87.13', 'article-title': 'Ivermectin, ‘wonder drug’ from Japan: the human use perspective', 'volume': '87', 'author': 'Crump', 'year': '2011', 'journal-title': 'Proc Jpn Acad Ser B Phys Biol Sci'}, { 'key': 'B10', 'doi-asserted-by': 'publisher', 'first-page': '1267', 'DOI': '10.3390/cells9051267', 'article-title': 'A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA ' 'Synthesis, Proofreading and Final Capping', 'volume': '9', 'author': 'Romano', 'year': '2020', 'journal-title': 'Cells'}, { 'key': 'B11', 'doi-asserted-by': 'publisher', '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'}, { 'key': 'B12', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/JVI.01925-19', 'article-title': 'Nucleocapsid Protein Recruitment to Replication-Transcription Complexes ' 'Plays a Crucial Role in Coronaviral Life Cycle', 'volume': '94', 'author': 'Cong', 'year': '2020', 'journal-title': 'J Virol'}, { 'key': 'B13', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/978-1-4615-5331-1_26', 'article-title': 'A new model for coronavirus transcription', 'volume': '440', 'author': 'Sawicki', 'year': '1998', 'journal-title': 'Adv Exp Med Biol'}, { 'key': 'B14', 'doi-asserted-by': 'publisher', 'first-page': '2991', 'DOI': '10.3390/v6082991', 'article-title': 'The coronavirus nucleocapsid is a multifunctional protein', 'volume': '6', 'author': 'McBride', 'year': '2014', 'journal-title': 'Viruses'}, { 'key': 'B15', 'doi-asserted-by': 'publisher', 'first-page': '6041', 'DOI': '10.1038/s41467-020-19843-1', 'article-title': 'Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich ' 'polymerase-containing condensates', 'volume': '11', 'author': 'Savastano', 'year': '2020', 'journal-title': 'Nat Commun'}, { 'key': 'B16', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.bbamcr.2011.03.019', 'article-title': 'Regulation of nucleocytoplasmic trafficking of viral proteins: an ' 'integral role in pathogenesis', 'volume': '1813', 'author': 'Fulcher', 'year': '2011', 'journal-title': 'Biochim Biophys Acta'}, { 'key': 'B17', 'doi-asserted-by': 'publisher', 'first-page': '75', 'DOI': '10.1042/bse0360075', 'article-title': 'Pore relations: nuclear pore complexes and nucleocytoplasmic exchange', 'volume': '36', 'author': 'Rout', 'year': '2000', 'journal-title': 'Essays Biochem'}, { 'key': 'B18', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00018-003-3070-3', 'article-title': 'Nucleocytoplasmic transport: taking an inventory', 'volume': '60', 'author': 'Fried', 'year': '2003', 'journal-title': 'Cell Mol Life Sci'}, { 'key': 'B19', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tcb.2004.07.016', 'article-title': 'Importin alpha: a multipurpose nuclear-transport receptor', 'volume': '14', 'author': 'Goldfarb', 'year': '2004', 'journal-title': 'Trends Cell Biol'}, { 'key': 'B20', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/s0092-8674(03)00082-5', 'article-title': 'Regulating access to the genome: nucleocytoplasmic transport throughout ' 'the cell cycle', 'volume': '112', 'author': 'Weis', 'year': '2003', 'journal-title': 'Cell'}, { 'key': 'B21', 'doi-asserted-by': 'publisher', 'first-page': '192', 'DOI': '10.1177/1087057110390360', 'article-title': 'An AlphaScreen®-based assay for high-throughput screening for specific ' 'inhibitors of nuclear import', 'volume': '16', 'author': 'Wagstaff', 'year': '2011', 'journal-title': 'J\xa0Biomol Screen'}, { 'key': 'B22', 'doi-asserted-by': 'publisher', 'DOI': '10.1073/pnas.2008176117', 'article-title': 'Genomic determinants of pathogenicity in SARS-CoV-2 and other human ' 'coronaviruses', 'volume': '117', 'author': 'Gussow', 'year': '2020', 'journal-title': 'Proc Natl Acad Sci USA'}, { 'key': 'B23', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/embo-reports/kvd092', 'article-title': 'Finding nuclear localization signals', 'volume': '1', 'author': 'Cokol', 'year': '2000', 'journal-title': 'EMBO Rep'}, { 'key': 'B24', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/JVI.75.19.9345-9356.2001', 'article-title': 'Localization to the nucleolus is a common feature of coronavirus ' 'nucleoproteins, and the protein may disrupt host cell division', 'volume': '75', 'author': 'Wurm', 'year': '2001', 'journal-title': 'J Virol'}, { 'key': 'B25', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/srep23138', 'article-title': 'Influenza A viruses escape from MxA restriction at the expense of ' 'efficient nuclear vRNP import', 'volume': '6', 'author': 'Gotz', 'year': '2016', 'journal-title': 'Sci Rep'}, { 'key': 'B26', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.bbrc.2020.04.136', 'article-title': 'Biochemical characterization of SARS-CoV-2 nucleocapsid protein', 'volume': '527', 'author': 'Zeng', 'year': '2020', 'journal-title': 'Biochem Biophys Res Commun'}, { 'key': 'B27', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.bbrc.2007.05.036', 'article-title': 'Trafficking motifs in the SARS-coronavirus nucleocapsid protein', 'volume': '358', 'author': 'You', 'year': '2007', 'journal-title': 'Biochem Biophys Res Commun'}, { 'key': 'B28', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/JVI.01275-13', 'article-title': 'Characterization of a critical interaction between the coronavirus ' 'nucleocapsid protein and nonstructural protein 3 of the viral ' 'replicase-transcriptase complex', 'volume': '87', 'author': 'Hurst', 'year': '2013', 'journal-title': 'J Virol'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'DOI': '10.2174/1568026617666170224122508', 'article-title': 'Influenza A Virus Nucleoprotein: A Highly Conserved Multi-Functional ' 'Viral Protein as a Hot Antiviral Drug Target', 'volume': '17', 'author': 'Hu', 'year': '2017', 'journal-title': 'Curr Top Med Chem'}, { 'key': 'B30', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/acs.jmedchem.9b01913', 'article-title': 'Structure-Based Stabilization of Non-native Protein-Protein ' 'Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug ' 'Design', 'volume': '63', 'author': 'Lin', 'year': '2020', 'journal-title': 'J Med Chem'}, { 'key': 'B31', 'doi-asserted-by': 'publisher', 'DOI': '10.1254/fpj.122.527', 'article-title': 'Pharmacological effects of ivermectin, an antiparasitic agent for ' 'intestinal strongyloidiasis: its mode of action and clinical efficacy', 'volume': '122', 'author': 'Ikeda', 'year': '2003', 'journal-title': 'Nihon Yakurigaku Zasshi'}, { 'key': 'B32', 'doi-asserted-by': 'publisher', 'DOI': '10.1208/s12248-007-9000-9', 'article-title': 'The pharmacokinetics and interactions of ivermectin in humans–a ' 'mini-review', 'volume': '10', 'author': 'González Canga', 'year': '2008', 'journal-title': 'AAPS J'}, { 'key': 'B33', 'article-title': 'Efficacy of ivermectin against ectoparasites of cattle in South Africa', 'volume': '56', 'author': 'Schröder', 'year': '1985', 'journal-title': 'J S Afr Vet Assoc'}, { 'key': 'B34', 'article-title': 'The multitargeted drug ivermectin: from an antiparasitic agent to a ' 'repositioned cancer drug', 'volume': '8', 'author': 'Juarez', 'year': '2018', 'journal-title': 'Am J Cancer Res'}, { 'key': 'B35', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s43440-020-00195-y', 'article-title': 'Ivermectin as a potential drug for treatment of COVID-19: an in-sync ' 'review with clinical and computational attributes', 'author': 'Kaur', 'year': '2021', 'journal-title': 'Pharmacol Rep'}, { 'key': 'B36', 'doi-asserted-by': 'publisher', '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': 'B37', 'doi-asserted-by': 'publisher', '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', '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': 'B39', 'doi-asserted-by': 'publisher', 'DOI': '10.2183/pjab.94.018', 'article-title': 'Importin α: functions as a nuclear transport factor and beyond', 'volume': '94', 'author': 'Oka', 'year': '2018', 'journal-title': 'Proc Jpn Acad Ser B Phys Biol Sci'}, { 'key': 'B40', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1742-4658.2011.08079.x', 'article-title': 'Targeted disruption of one of the importin α family members leads to ' 'female functional incompetence in delivery', 'volume': '278', 'author': 'Moriyama', 'year': '2011', 'journal-title': 'FEBS J'}, { 'key': 'B41', 'doi-asserted-by': 'publisher', 'DOI': '10.1515/hsz-2015-0171', 'article-title': 'The importin α/β-specific inhibitor Ivermectin affects HIF-dependent ' 'hypoxia response pathways', 'volume': '396', 'author': 'Kosyna', 'year': '2015', 'journal-title': 'Biol Chem'}, {'key': 'B42', 'unstructured': 'TABLETS; STROMECTOL®(IVERMECTIN) (MERCK)'}, { 'key': 'B43', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1080/07391102.2020.1839564', 'article-title': 'Binding mechanism and structural insights into the identified protein ' 'target of COVID-19 and importin-α with', 'author': 'Sen Gupta', 'year': '2020', 'journal-title': 'J Biomol Struct Dyn'}, { 'key': 'B44', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00011-008-8007-8', 'article-title': 'Ivermectin inhibits LPS-induced production of inflammatory cytokines ' 'and improves LPS-induced survival in mice', 'volume': '57', 'author': 'Zhang', 'year': '2008', 'journal-title': 'Inflamm Res'}, { 'key': 'B45', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.11.21.392639', 'article-title': 'Anti-COVD-19 efficacy of ivermectin in the golden hamster', 'author': 'de Melo', 'year': '2020', 'journal-title': 'BioRxiv'}, { 'key': 'B46', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0242184', 'article-title': 'Lack of efficacy of standard doses of ivermectin in severe COVID-19 ' 'patients', 'volume': '15', 'author': 'Camprubí', 'year': '2020', 'journal-title': 'PloS One'}, { 'key': 'B47', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2020.01196', 'article-title': 'COVID-19 Therapeutic Options Under Investigation', 'volume': '11', 'author': 'Kaddoura', 'year': '2020', 'journal-title': 'Front Pharmacol'}, { 'key': 'B48', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/infdis/170.3.663', 'article-title': 'C-reactive protein and interleukin-6 are elevated in onchocerciasis ' 'patients after ivermectin treatment', 'volume': '170', 'author': 'Njoo', 'year': '1994', 'journal-title': 'J Infect Dis'}, { 'key': 'B49', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/009127002401382731', 'article-title': 'Safety, tolerability, and pharmacokinetics of escalating high doses of ' 'ivermectin in healthy adult subjects', 'volume': '42', 'author': 'Guzzo', 'year': '2002', 'journal-title': 'J Clin Pharmacol'}, { 'key': 'B50', 'first-page': '493', 'article-title': 'Reactions in dogs given ivermectin', 'volume': '183', 'author': 'Seward', 'year': '1983', 'journal-title': 'J Am Vet Med Assoc'}, { 'key': 'B51', 'doi-asserted-by': 'publisher', 'first-page': '342', 'DOI': '10.1016/s0035-9203(98)91035-5', 'article-title': 'Absence of ivermectin-associated excess deaths', 'volume': '92', 'author': 'Alexander', 'year': '1998', 'journal-title': 'Trans R Soc Trop Med Hyg'}, { 'key': 'B52', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2020.11.191', 'article-title': 'A five-day course of ivermectin for the treatment of COVID-19 may ' 'reduce the duration of illness', 'volume': '103', 'author': 'Ahmed', 'year': '2020', 'journal-title': 'Int J Infect Dis'}, { 'key': 'B53', 'doi-asserted-by': 'publisher', 'first-page': '85', 'DOI': '10.1016/j.chest.2020.10.009', 'article-title': 'Use of Ivermectin Is Associated With Lower Mortality in Hospitalized ' 'Patients With Coronavirus Disease 2019: The Ivermectin in COVID ' 'Nineteen Study', 'volume': '159', 'author': 'Rajter', 'year': '2021', 'journal-title': 'Chest'}, { 'key': 'B54', 'doi-asserted-by': 'publisher', 'first-page': '498', 'DOI': '10.1186/s13063-020-04421-z', 'article-title': 'The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate ' 'the Potential of Ivermectin to Reduce COVID-19 Transmission in low ' 'risk, non-severe COVID-19 patients in the first 48 hours after symptoms ' 'onset: A structured summary of a study protocol for a randomized ' 'control pilot trial', 'volume': '21', 'author': 'Chaccour', 'year': '2020', 'journal-title': 'Trials'}, { 'key': 'B55', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/mBio.00221-18', 'article-title': 'Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is ' 'Mediated by the Viral Polymerase and the Proofreading Exoribonuclease', 'volume': '9', 'author': 'Agostini', 'year': '2018', 'journal-title': 'mBio'}, { 'key': 'B56', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the Treatment of Covid-19 - Final Report', 'volume': '383', 'author': 'Beigel', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'B57', 'doi-asserted-by': 'publisher', 'first-page': '497', 'DOI': '10.1056/NEJMoa2023184', 'article-title': 'Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial ' 'Results', 'volume': '384', 'author': 'Pan', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'B58', 'doi-asserted-by': 'publisher', 'article-title': 'Remdesivir-Ivermectin combination displays synergistic interaction with ' 'improved in vitro antiviral activity against SARS-CoV-2', 'author': 'Jeffreys', 'year': '2020', 'DOI': '10.1101/2020.12.23.424232'}, { 'key': 'B59', 'doi-asserted-by': 'publisher', 'first-page': '693', 'DOI': '10.1056/NEJMoa2021436', 'article-title': 'Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary ' 'Report', 'volume': '384', 'author': 'Horby', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'B60', 'volume-title': 'Recovery Trial Closes Recruitment to Convalescent Plasma Treatment for ' 'Patients Hospitalised with COVID-19', 'year': '2021'}, { 'key': 'B61', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2035002', 'article-title': 'REGN-COV2, a Neutralizing Antibody CocktailOutpatients with Covid-19', 'volume': '384', 'author': 'Weinreich', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': 'B62', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2029849', 'article-title': 'SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19', 'volume': '384', 'author': 'Chen', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': 'B63', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2100433', 'article-title': 'Interleukin-6 Receptor Antagonists in Critically Ill Patients with ' 'Covid-19 –Preliminary report', 'author': 'Gordon', 'year': '2021', 'journal-title': 'N Engl J Med'}, { 'key': 'B64', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/00042560-199510001-00007', 'article-title': 'Viral resistance and the selection of antiretroviral combinations', 'volume': '10', 'author': 'Larder', 'year': '1995', 'journal-title': 'J\xa0Acquir Immune Defic Syndr Hum Retrovirol'}, { 'key': 'B65', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fmicb.2020.01818', 'article-title': 'Antivirals Against Coronaviruses: Candidate Drugs for SARS-CoV-2 ' 'Treatment', 'volume': '11', 'author': 'Santos', 'year': '2020', 'journal-title': 'Front Microbiol'}], 'container-title': 'Frontiers in Immunology', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fimmu.2021.663586/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 3, 30]], 'date-time': '2021-03-30T13:12:14Z', 'timestamp': 1617109934000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fimmu.2021.663586/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 3, 30]]}, 'references-count': 65, 'alternative-id': ['10.3389/fimmu.2021.663586'], 'URL': 'http://dx.doi.org/10.3389/fimmu.2021.663586', 'relation': {}, 'ISSN': ['1664-3224'], 'subject': [], 'container-title-short': 'Front. Immunol.', 'published': {'date-parts': [[2021, 3, 30]]}}
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