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. 2023 Mar:32:164-166.
doi: 10.1016/j.jgar.2022.11.011. Epub 2022 Dec 1.

Effect of farnesyltransferase inhibitors on SARS-CoV-2

Lea Weber  1 , Lena Mautner  2 , Mona Hoyos  2 , Anja Ehrhardt  3 , Armin Baiker  2 , Hagen Sjard Bachmann  4
Affiliations

Effect of farnesyltransferase inhibitors on SARS-CoV-2

Lea Weber et al. J Glob Antimicrob Resist. 2023 Mar.

Abstract

Objectives: The emergence of SARS-CoV-2 in 2019 led to a severe pandemic situation. Treatment options are limited, and the efficacy of vaccines decreases due to mutations in SARS-CoV-2 strains. Therefore, new treatment options are urgently needed, and computational compound screenings are used to predict drugs quickly. One of these screenings revealed farnesyltransferase inhibitors (FTIs) as potential candidates.

Methods: SARS-CoV-2 infected Calu-3 cells were treated with lonafarnib and tipifarnib and fold change viral replication of SARS-CoV-2 was measured using RT-qPCR. Furthermore, morphological changes, like CPE formation, were evaluated. Effects on Calu-3 cells were analyzed using MTT assay.

Results: We demonstrated that the FTIs lonafarnib and tipifarnib have an effect on SARS-CoV-2 Wildtype and the Delta variant. Both FTIs dose-dependently reduced morphological changes and the formation of cytopathic effects in SARS-CoV-2 infected Calu-3 cells. The effect of the FTIs on Omicron needs to be further elucidated because of inefficient viral replication.

Conclusions: The FTI lonafarnib and tipifarnib might be effective drugs against different SARS-CoV-2 strains.

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Conflict of interest statement

Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig 1:
Fig. 1
(A) Representative morphological images of SARS-CoV-2 infected Calu-3 cells after treatment with lonafarnib and tipifarnib for 30 h. Cells infected with Wildtype, Delta or Omicron were treated with lonafarnib and tipifarnib (0.1 µM, 20 µM, and 30 µM), DMSO and Remdesivir (2 µM) as controls. Scale bar: 300 µM. (B)–(C) Cell viability test on Calu-3 cells after treatment with lonafarnib (B) and tipifarnib (C). Cells were incubated with lonafarnib and tipifarnib in different concentrations, ranging from 0.1 µM–50 µM for 48 h. (D)–(I) Effect of FTIs on fold change viral replication of SARS-CoV-2 on Calu-3 cells. Effect of lonafarnib (left) and tipifarnib (right) on Wildtype (D, E), Delta (F, G) and Omicron (H, I). A triangle for the fold-change in viral replication for remdesivir was added in (D)–(I). DMSO, Dimethyl sulfoxide; FTI, Farnesyltransferase inhibitor; Wildtype, SARS-CoV-2 non-VOC/B.1.1; Delta, SARS-CoV-2 Delta/B.1.617.2; Omicron, SARS-CoV-2 Omicron/B.1.1.529.
See this image and copyright information in PMC

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