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All Studies   Meta Analysis    Recent:   

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445
Apr 2022  
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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
In Vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results for CQ and remdesivir.
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.
Study covers ivermectin, HCQ, and remdesivir.
Delandre et al., 2 Apr 2022, peer-reviewed, 12 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants
Océane Delandre, Mathieu Gendrot, Priscilla Jardot, Marion Le Bideau, Manon Boxberger, Céline Boschi, Isabelle Fonta, Joel Mosnier, Sébastien Hutter, Anthony Levasseur, Bernard La Scola, Bruno Pradines
Pharmaceuticals, doi:10.3390/ph15040445
Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10 −34 ) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10 −13 ). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.
Supplementary Materials: The following supporting information can be downloaded at: www.mdpi.com/article/10.3390/ph15040445/s1, Table S1 : List of nucleotide and amino acid changes associated with the different SARS-CoV-2 variants. Conflicts of Interest: The authors declare no conflicts of interest. The findings and conclusion of this report are those of the authors and do not represent the views of the Ministère des Armées and Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation.
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{ 'indexed': {'date-parts': [[2024, 2, 9]], 'date-time': '2024-02-09T13:19:30Z', 'timestamp': 1707484770021}, 'reference-count': 110, 'publisher': 'MDPI AG', 'issue': '4', 'license': [ { 'start': { 'date-parts': [[2022, 4, 2]], 'date-time': '2022-04-02T00:00:00Z', 'timestamp': 1648857600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100001665', 'name': 'French National Research Agency', 'doi-asserted-by': 'publisher', 'award': ["Investissement d'avenir ANR-10-IAHU-03"]}, {'name': 'Institut hospitalo-universitaire Méditerranée Infection', 'award': ['COVID-19']}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Over the past two years, several variants of SARS-CoV-2 have emerged and spread all ' 'over the world. However, infectivity, clinical severity, re-infection, virulence, ' 'transmissibility, vaccine responses and escape, and epidemiological aspects have differed ' 'between SARS-CoV-2 variants. Currently, very few treatments are recommended against ' 'SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a ' 'rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. ' 'Ivermectin is an antihelminthic agent that previously showed in vitro effects against a ' 'SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated ' 'the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated ' 'SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging ' 'to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and ' 'omicron). The in vitro activity of ivermectin was compared to those of chloroquine and ' 'remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 ' 'from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro ' 'activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ' '± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, ' 'mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = ' '214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10−34) and remdesivir (No. EC50 = 201, mean EC50 = ' '11.9 ± 10.0 µM) (p = 1.6 × 10−13). These results should be interpreted with caution regarding ' 'the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate ' 'in vitro study results into actual clinical treatment in patients.</jats:p>', 'DOI': '10.3390/ph15040445', 'type': 'journal-article', 'created': {'date-parts': [[2022, 4, 3]], 'date-time': '2022-04-03T06:59:52Z', 'timestamp': 1648969192000}, 'page': '445', 'source': 'Crossref', 'is-referenced-by-count': 6, 'title': 'Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains ' 'Belonging to 14 Variants', 'prefix': '10.3390', 'volume': '15', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-8794-8923', 'authenticated-orcid': False, 'given': 'Océane', 'family': 'Delandre', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-2322-5427', 'authenticated-orcid': False, 'given': 'Mathieu', 'family': 'Gendrot', 'sequence': 'additional', 'affiliation': []}, {'given': 'Priscilla', 'family': 'Jardot', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marion', 'family': 'Le Bideau', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7740-0518', 'authenticated-orcid': False, 'given': 'Manon', 'family': 'Boxberger', 'sequence': 'additional', 'affiliation': []}, {'given': 'Céline', 'family': 'Boschi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Isabelle', 'family': 'Fonta', 'sequence': 'additional', 'affiliation': []}, {'given': 'Joel', 'family': 'Mosnier', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sébastien', 'family': 'Hutter', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anthony', 'family': 'Levasseur', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-8006-7704', 'authenticated-orcid': False, 'given': 'Bernard', 'family': 'La Scola', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-2360-3803', 'authenticated-orcid': False, 'given': 'Bruno', 'family': 'Pradines', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2022, 4, 2]]}, 'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-020-2008-3'}, {'key': 'ref2', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12985-021-01633-w'}, {'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/20499361211024372'}, {'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jaip.2021.07.016'}, {'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijbiomac.2021.08.076'}, {'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2020.101873'}, {'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2020.08.032'}, {'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41422-020-0282-0'}, {'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/microorganisms8121872'}, {'key': 'ref10', 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Rep.'}, {'key': 'ref66', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijbiomac.2020.08.166'}, {'key': 'ref67', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.106119'}, {'key': 'ref68', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2022.01.03.21268111'}, {'key': 'ref69', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.105932'}, {'key': 'ref70', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijantimicag.2020.105938'}, {'key': 'ref71', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.heliyon.2020.e04900'}, {'key': 'ref72', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2019.104541'}, {'key': 'ref73', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/molecules26247438'}, {'key': 'ref74', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-021-02972-y'}, {'key': 'ref75', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s11030-020-10178-z'}, {'key': 'ref76', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ejphar.2020.173430'}, {'key': 'ref77', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.molstruc.2021.132041'}, {'key': 'ref78', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/BF01839186'}, {'key': 'ref79', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/bcp.14476'}, {'key': 'ref80', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.xphs.2020.08.024'}, {'key': 'ref81', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/cpt.1889'}, {'key': 'ref82', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2021.625678'}, {'key': 'ref83', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/cpt.1909'}, {'key': 'ref84', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v13102084'}, {'key': 'ref85', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/03000605211013550'}, {'key': 'ref86', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.07.07.20145979'}, {'key': 'ref87', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-020-74084-y'}, {'key': 'ref88', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.xphs.2021.01.017'}, {'key': 'ref89', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0242184'}, {'key': 'ref90', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/20477724.2021.1890887'}, {'key': 'ref91', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2021.01.05.21249310'}, {'key': 'ref92', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12879-021-06348-5'}, {'key': 'ref93', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2021.3071'}, {'key': 'ref94', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jiac.2021.08.021'}, {'key': 'ref95', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamainternmed.2022.0189'}, {'key': 'ref96', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2021.02.014'}, {'key': 'ref97', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eclinm.2020.100720'}, {'key': 'ref98', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/jmv.27469'}, {'key': 'ref99', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.chest.2020.10.009'}, {'key': 'ref100', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ofid/ofab645'}, {'key': 'ref101', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jclinepi.2021.12.018'}, {'key': 'ref102', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ofid/ofab358'}, {'key': 'ref103', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.meegid.2021.105092'}, {'key': 'ref104', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2021.101980'}, {'key': 'ref105', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2021.03.068'}, {'key': 'ref106', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cmi.2021.05.006'}, {'key': 'ref107', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2021.102085'}, {'key': 'ref108', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s10096-020-04106-0'}, {'key': 'ref109', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tice.2021.101497'}, {'key': 'ref110', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tmaid.2020.101632'}], 'container-title': 'Pharmaceuticals', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/1424-8247/15/4/445/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 4, 5]], 'date-time': '2022-04-05T10:25:31Z', 'timestamp': 1649154331000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/1424-8247/15/4/445'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 4, 2]]}, 'references-count': 110, 'journal-issue': {'issue': '4', 'published-online': {'date-parts': [[2022, 4]]}}, 'alternative-id': ['ph15040445'], 'URL': 'http://dx.doi.org/10.3390/ph15040445', 'relation': {}, 'ISSN': ['1424-8247'], 'subject': [], 'container-title-short': 'Pharmaceuticals', 'published': {'date-parts': [[2022, 4, 2]]}}
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