Jeffreys: Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Jeffreys et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (date from earlier preprint) (In Vitro)

Jeffreys et al., Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against.., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (date from earlier preprint) (In Vitro)

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In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination.

15 In Vitro studies support the efficacy of ivermectin [Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag].

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1. Boschi et al., bioRxiv, doi:10.1101/2022.11.24.517882, SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects, https://www.biorxiv.org/content/10.1101/2022.11.24.517882.

2. Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, https://www.sciencedirect.com/science/article/pii/S0166354220302011.

3. Croci et al., International Journal of Biomaterials, doi:10.1155/2016/8043983, Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin, http://www.hindawi.com/journals/ijbm/2016/8043983/.

4. De Forni et al., PLoS ONE, doi:10.1371/journal.pone.0276751, Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients, https://journals.plos.org/plosone/..le?id=10.1371/journal.pone.0276751.

5. Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445, Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, https://www.mdpi.com/1424-8247/15/4/445.

6. Jeffreys et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (preprint 12/24/2020), Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2, https://www.sciencedirect.com/science/article/pii/S0924857922000309.

7. Jitobaom et al., BMC Pharmacology and Toxicology, doi:10.1186/s40360-022-00580-8 (preprint 11/30/2021), Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations, https://bmcpharmacoltoxicol.biomed..rticles/10.1186/s40360-022-00580-8.

8. Jitobaom (B) et al., Research Square, doi:10.21203/rs.3.rs-941811/v1, Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2, https://www.researchsquare.com/article/rs-941811/v1.

9. Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055, Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment, https://onlinelibrary.wiley.com/doi/10.1002/jcp.30055.

10. Liu et al., bioRxiv, doi:10.1101/2022.01.20.477147, SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level, https://www.biorxiv.org/content/10.1101/2022.01.20.477147.

11. Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x, Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents, https://www.nature.com/articles/s42003-020-01577-x.

12. Mountain Valley MD, Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™, https://www.globenewswire.com/en/n..ariants-Tested-With-Ivectosol.html.

13. Segatori et al., Viruses, doi:10.3390/v13102084, Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients, https://www.mdpi.com/1999-4915/13/10/2084.

14. Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179, Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19, https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00179.

15. Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384, Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro, https://www.sciencedirect.com/science/article/pii/S0168170221000915.

Jeffreys et al., 24 Dec 2020, peer-reviewed, 17 authors.

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

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Abstract: In vitro synergistic interaction of remdesivir and ivermectin against SARS-CoV-2 Editor: Dr Jim Gray Journal Pre-proof Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2 Laura N Jeffreys , Shaun H Pennington , Jack Duggan , Claire H Caygill , Rose C Lopeman , Alastair F Breen , Jessica B Jinks , Alison Ardrey , Samantha Donnellan , Edward I Patterson , Grant L Hughes , David W Hong , Paul M O’Neill , Ghaith Aljayyoussi , Andrew Owen , Stephen A Ward , Giancarlo A Biagini PII: DOI: Reference: S0924-8579(22)00030-9 https://doi.org/10.1016/j.ijantimicag.2022.106542 ANTAGE 106542 To appear in: International Journal of Antimicrobial Agents Received date: Accepted date: 9 September 2021 20 January 2022 Please cite this article as: Laura N Jeffreys , Shaun H Pennington , Jack Duggan , Claire H Caygill , Rose C Lopeman , Alastair F Breen , Jessica B Jinks , Alison Ardrey , Samantha Donnellan , Edward I Patterson , Grant L Hughes , David W Hong , Paul M O’Neill , Ghaith Aljayyoussi , Andrew Owen , Stephen A Ward , Giancarlo A Biagini , Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2, International Journal of Antimicrobial Agents (2022), doi: https://doi.org/10.1016/j.ijantimicag.2022.106542 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2022 Published by Elsevier Ltd. FULL TITLE Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2 SHORT TITLE In vitro synergistic interaction of remdesivir and ivermectin against SARS-CoV-2 AUTHORS Laura N Jeffreys1*, Shaun H Pennington1*‡, Jack Duggan1, Claire H Caygill, Rose C Lopeman, Alastair F Breen1, Jessica B Jinks1, Alison Ardrey1, Samantha Donnellan1, Edward I Patterson1,2, Grant L Hughes1,2, David W Hong3, Paul M O’Neill3, Ghaith Aljayyoussi1, Andrew Owen4, Stephen A Ward1 and Giancarlo A Biagini1*‡ 1 Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK 2 Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK 3 Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, U.K. 4 Department of Pharmacology and Therapeutics, Centre of Excellence in Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, L69 3GE, UK. 1 * JOINT FIRST AUTHORS ‡CO-CORRESPONDING AUTHORS Giancarlo A Biagini Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK +44151 705 3151 giancarlo.biagini@lstmed.ac.uk Shaun H Pennington Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK +44151 702 9427 shaun.pennington@lstmed.ac.uk ABSTRACT WORD COUNT: 130 MAIN DOCUMENT WORD..

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