In vitro evaluation of the activity of teriflunomide against SARS-CoV-2 and the human coronaviruses 229E and OC43.

Autor: Lang P; Sanofi, 153/211 Second Avenue, Waltham, MA, 02451, USA., Geertsen SS; Sanofi, 450 Water Street, Cambridge, MA, 02141, USA., Lublin AL; Sanofi, 450 Water Street, Cambridge, MA, 02141, USA., Potter MC; Sanofi, 450 Water Street, Cambridge, MA, 02141, USA., Gladysheva T; Sanofi, 153/211 Second Avenue, Waltham, MA, 02451, USA., Gregory JS; Sanofi, 153/211 Second Avenue, Waltham, MA, 02451, USA., Rufi P; Sanofi, 1 Av. Pierre Brossolette, 91380, Chilly-Mazarin, France.
Jazyk: angličtina
Zdroj: Biochemistry and biophysics reports [Biochem Biophys Rep] 2023 Mar; Vol. 33, pp. 101395. Date of Electronic Publication: 2022 Nov 23.
DOI: 10.1016/j.bbrep.2022.101395
Abstrakt: Previous data have suggested an antiviral effect of teriflunomide, including against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent underlying the ongoing COVID-19 pandemic. We undertook an in vitro investigation to evaluate the inhibitory activity of teriflunomide against SARS-CoV-2 in a cell-based assay. Teriflunomide was added to Vero (kidney epithelial) cells that had been infected with SARS-CoV-2. A nucleocapsid immunofluorescence assay was performed to examine viral inhibition with teriflunomide and any potential cytotoxic effect. The 50% effective concentration (EC 50 ) for teriflunomide against SARS-CoV-2 was 15.22 μM. No cytotoxicity was evident for teriflunomide in the Vero cells (i.e., the 50% cytotoxic concentration [CC 50 ] was greater than the highest test concentration of 100 μM). The data were supported by additional experiments using other coronaviruses and human cell lines. In the SARS-CoV-2-infected Vero cells, the prodrug leflunomide had an EC 50 of 16.49 μM and a CC 50 of 54.80 μM. Our finding of teriflunomide-mediated inhibition of SARS-CoV-2 infection at double-digit micromolar potency adds to a growing body of evidence for a broad-ranging antiviral effect of teriflunomide.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul Lang, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Paul Lang, PhD reports a relationship with Sanofi that includes: employment. Svend S. Geertsen, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Svend S. Geertsen, PhD reports a relationship with Sanofi that includes: employment. Alex L. Lublin, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Alex L. Lublin, PhD reports a relationship with Sanofi that includes: employment. Michelle C. Potter, PhD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Michelle C. Potter, PhD reports a relationship with Sanofi that includes: employment. Tatiana Gladysheva reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Tatiana Gladysheva reports a relationship with Sanofi that includes: employment. Jill S. Gregory reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Jill S. Gregory reports a relationship with Sanofi that includes: employment. Pascal Rufi, MD reports writing assistance was provided by Elevate Scientific Affairs, Envision Pharma Group. Pascal Rufi, MD reports a relationship with Sanofi that includes: employment.
(© 2022 Published by Elsevier B.V.)
Databáze: MEDLINE
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