Effect of farnesyltransferase inhibitors on SARS-CoV-2

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.