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The following is a summary of “Remdesivir is active in vitro against tick-borne encephalitis virus and selects for resistance mutations in the viral RNA-dependent RNA polymerase,” published in the February 2025 issue of Infectious Diseases by Nyström et al.
Tick-borne encephalitis (TBE) is a neurological disease caused by the tick-borne encephalitis virus (TBEV), with some fatal breakthrough infections occurring despite vaccination.
Researchers conducted a retrospective study to estimate the in vitro activity of licensed remdesivir (RDV) and sofosbuvir (SOF) for potential repurposing against TBEV in the absence of approved antiviral therapy.
They cultured TBEV in A549 cells and assessed the inhibitory effects of RDV; GS-5734, its parent nucleotide GS-441524, and SOF; GS-7977. RDV (GS-5734), GS-441524, and SOF (GS-7977) were synthesized and supplied by Gilead Sciences (Foster City, California, USA). Investigators remained blinded to the compound names and suspected mechanisms of action until all experiments were completed.
The results showed that after 78 hours, RDV had significantly lower half-maximal effective concentration (EC50) values than SOF (0.14 vs 11 µM) based on TBEV RNA levels measured by RT-qPCR. The RDV also exhibited a lower mean EC50 (0.55 µM) compared to GS-441524 (>8.9 µM) and SOF (13.1 µM) using crystal violet staining after 5 days. After 11 passages of TBEV in the presence of RDV, a virus variant emerged with a higher EC50 (1.32 vs 0.55 µM), showing 2 mutations (L3122F and Y3278F) in NS5, the viral RNA-dependent RNA polymerase (RdRp), and 1 substitution in the envelope (E) protein (E402G). Similarly, SOF resistance emerged after 20 passages, increasing EC50 values from 10 µM to 35.5 µM.
Investigators concluded that RDV demonstrated strong antiviral activity against TBEV in test tubes by specifically targeting the viral RdRp, which was supported by the development of resistance-related NS5 double substitutions when RDV was present.
Source: tandfonline.com/doi/full/10.1080/23744235.2025.2468510#abstract
