Delandre: Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants [HCQ]

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 (In Vitro)

Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14.., Pharmaceuticals, doi:10.3390/ph15040445 (In Vitro)

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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.

CQ showed better efficacy for omicron compared to most other variants.

14 In Vitro studies support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].

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1. Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, https://www.sciencedirect.com/science/article/pii/S0882401020305155.

2. Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31), Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, https://www.frontiersin.org/articl..ign=ECO_FCIMB_XXXXXXXX_auto-dlvrit.

3. Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741, Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, https://www.biorxiv.org/content/10.1101/2021.03.16.435741v1.

4. 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.

5. Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877, Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, https://www.mdpi.com/1999-4923/14/4/877.

6. Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, https://www.nature.com/articles/s41586-020-2575-3.

7. Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, https://www.nature.com/articles/s41421-020-0156-0.

8. Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22), Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, https://journals.plos.org/plospath..le?id=10.1371/journal.ppat.1009212.

9. Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302, An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, https://journals.plos.org/plosone/..le?id=10.1371/journal.pone.0252302.

10. Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892, A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, https://www.biorxiv.org/content/10.1101/2020.08.02.232892v1.

11. Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333, Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467095/.

12. Wang (B) et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, https://www.nature.com/articles/s4..iVs8_7R1KkwOuqjRhx7psfHV6iSDRD1cM0.

13. Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), https://academic.oup.com/cid/advan..le/doi/10.1093/cid/ciaa237/5801998.

14. Yuan et al., Communications Biology, doi:10.1038/s42003-022-03841-8, Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, https://www.nature.com/articles/s42003-022-03841-8.

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.

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Abstract: Article Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants Océane Delandre 1,2,3, Mathieu Gendrot 1,2,3, Priscilla Jardot 3,4, Marion Le Bideau 3,4, Manon Boxberger 3,4, Céline Boschi 3,4, Isabelle Fonta 1,2,3,5, Joel Mosnier 1,2,3,5, Sébastien Hutter 2,3, Anthony Levasseur 3,4, Bernard La Scola 3,4 and Bruno Pradines 1,2,3,5,* Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France; o.delandre@gmail.com (O.D.); ma.gendrot@laposte.net (M.G.); isabelle.fonta.09@gmail.com (I.F.); joelmosnier@orange.fr (J.M.) 2 Aix Marseille University, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France; sebastien.hutter@univ-amu.fr 3 IHU Méditerranée Infection, 13005 Marseille, France; priscilla.jardot@univ-amu.fr (P.J.); marion.le-bideau@ap-hm.fr (M.L.B.); manon.boxberger@hotmail.fr (M.B.); celine.boschi@ap-hm.fr (C.B.); anthony.levasseur@univ-amu.fr (A.L.); bernard.la-scola@univ-amu.fr (B.L.S.) 4 Aix Marseille University, IRD, AP-HM, MEPHI, 13005 Marseille, France 5 Centre National de Référence du Paludisme, 13005 Marseille, France * Correspondence: bruno.pradines@gmail.com 1 Citation: Delandre, O.; Gendrot, M.; Jardot, P.; Le Bideau, M.; Boxberger, M.; Boschi, C.; Fonta, I.; Mosnier, J.; Hutter, S.; Levasseur, A.; et al. Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants. Pharmaceuticals 2022, 15, 445. https://doi.org/10.3390/ph15040445 Academic Editors: Zoidis Grigoris and Serena Massari Received: 3 February 2022 Accepted: 30 March 2022 Published: 2 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional Abstract: 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..

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