Tang et al.
Inhibition of tick-borne encephalitis virus in cell cultures by ribavirin
Front Microbiol. 2023;14:1182798. doi:10.3389/fmicb.2023.1182798
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.
Ribavirin, a synthetic guanosin nucleoside analog has some anticancer and antiviral properties and is known as a chemotherapeutic agent with activities against a wide range of RNA and DNA viruses. Although ribavirin has been assessed as a safe antiviral drug, the effectiveness against viruses remains to be validated and the precise mechanisms of ribavirin action are still not completely understood. In a recent study, the influence of ribavirin on TBE virus propagation was evaluated in susceptible human cell lines.
The cytotoxicity of ribavirin was tested on various cell lines, and it was, for example, not toxic even in high concentrations on Vero cells (300 mg/ml) or on the human hepatoma cell line Huh7.5.1 (100 mg/ml).
In A549 cells, TBE virus protein expression showed significant inhibition at concentrations of 40–60 mg/ml), and treatment with 60 mg/ml led to nearly a complete inhibition of TBE virus infection. Ribavirin also reduced TBE virus titers in SH-SY5Y cells in a dose-dependent manner. TBE virus titers and RNA levels were significantly reduced in co-treatment, post-treatment, and pre-treatment in both cell lines.
Ribavirin had a positive effect on the protein expression of the human IFN-induced dynamin-like GTPase MxA, which has broad antiviral activity, indicating that ribavirin may exhibit anti-TBE virus action through induction of cellular antiviral response.
It is known that serum levels of TNF-a are increased in TBE patients. Ribavirin significantly inhibited the production of TNF-a and IL-1b at the scheme of post-treatment. The results showed that suppression of TBE virus induced TNF-a release by ribavirin may attenuate inflammation via controlling pro-inflammatory cytokine-mediated immunoinflammatory events.
Molecular bases of antiviral effects of ribavirin on TBE virus need to be further investigated based on different virulent strains and suitable animal models. Ribavirin might present a promising and effective antiviral drug against TBE virus.