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In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2.
Antiviral Res. 2020 09; 181:104878.AR

Abstract

In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.

Authors+Show Affiliations

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; Signia Therapeutics SAS, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; Laboratoire de Virologie, Centre National de Référence des Virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. Electronic address: manuel.rosa-calatrava@univ-lyon1.fr.CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France. Electronic address: olivier.terrier@univ-lyon1.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32679055

Citation

Pizzorno, Andrés, et al. "In Vitro Evaluation of Antiviral Activity of Single and Combined Repurposable Drugs Against SARS-CoV-2." Antiviral Research, vol. 181, 2020, p. 104878.
Pizzorno A, Padey B, Dubois J, et al. In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. Antiviral Res. 2020;181:104878.
Pizzorno, A., Padey, B., Dubois, J., Julien, T., Traversier, A., Dulière, V., Brun, P., Lina, B., Rosa-Calatrava, M., & Terrier, O. (2020). In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. Antiviral Research, 181, 104878. https://doi.org/10.1016/j.antiviral.2020.104878
Pizzorno A, et al. In Vitro Evaluation of Antiviral Activity of Single and Combined Repurposable Drugs Against SARS-CoV-2. Antiviral Res. 2020;181:104878. PubMed PMID: 32679055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. AU - Pizzorno,Andrés, AU - Padey,Blandine, AU - Dubois,Julia, AU - Julien,Thomas, AU - Traversier,Aurélien, AU - Dulière,Victoria, AU - Brun,Pauline, AU - Lina,Bruno, AU - Rosa-Calatrava,Manuel, AU - Terrier,Olivier, Y1 - 2020/07/15/ PY - 2020/05/06/received PY - 2020/07/06/revised PY - 2020/07/07/accepted PY - 2020/7/18/pubmed PY - 2020/9/8/medline PY - 2020/7/18/entrez KW - Antivirals KW - Berberine KW - COVID-19 KW - Diltiazem KW - Drug combination KW - Remdesivir SP - 104878 EP - 104878 JF - Antiviral research JO - Antiviral Res VL - 181 N2 - In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/32679055/In_vitro_evaluation_of_antiviral_activity_of_single_and_combined_repurposable_drugs_against_SARS_CoV_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(20)30292-8 DB - PRIME DP - Unbound Medicine ER -