Binderup et al.
Differential activity of nucleotide analogs against tick-borne encephalitis and yellow fever viruses in human cell lines
Virology. 2023;585:179-185. doi:10.1016/j.virol.2023.06.002

There are no specific antiviral drugs available for TBE virus infections (see e.g., Snapshot week 2/2023). Various nucleoside analogs have been tested, among which are galidesivir and ribavirin.

Recently, ribavirin, a synthetic guanosine nucleoside analog which has some anticancer and antiviral properties and is known as a chemotherapeutic agent with activities against a wide range of RNA and DNA viruses, has been tested in cell lines as drug against TBE (see Snapshot week 32/2023). Now, a panel of nucleoside/nucleotide analogs (nucs) have been tested in various human cell lines for activity against TBE virus and yellow fever virus.

After an initial screening with 14 nucs, eight drugs were found active against TBE virus and yellow fever virus: remdesivir, GS-6620, sofosbuvir, uprifosbuvir, valopicitabine, galidesivir, ribavirin and molnupiravir.

It was noticed that antiviral activity was cell-type dependent, most likely due to differences in metabolic activation between cell lines. Discrepancies between EC50 values obtained here and previously reported were found, which emphasizes the difficulties of comparing drug activity due to differences in experimental systems and methodologies, e.g., ribavirin exhibited only moderate antiviral activity (which contrasts with Snapshot week 32/2023).

Remdesivir, sofosbuvir and uprifosbuvir were highly active against both viruses in Huh7.5 cells (uprifosbuvir already underwent clinical phase 3 studies for treatment of HCV). The highly potent remdesivir has however been associated with liver injury in a few COVID-19 patients.

The authors concluded that the best drug candidates against TBE virus and yellow fever virus may be remdesivir, sofosbuvir and uprifosbuvir. These compounds, originally found to inhibit HCV, and sofosbuvir and remdesivir currently used to treat chronic hepatitis C and COVID-19, respectively, could easily be repurposed for their use against TBE virus or yellow virus infection and merit further investigations in clinical studies.

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