Goryashchenko et al.
Discovery of small molecule antivirals targeting tick-borne encephalitis virus
Ann Rep Med Chem. 2022;58:1-54. doi:10.1016/bs.armc.2022.08.007

Currently, there are no specific small molecules (antivirals) licensed to treat TBE and other flaviviral diseases, and therefore patient care is mainly symptomatic and supportive. A Russian team has now presented an overview about the efforts to discover lead substances inhibiting TBE virus replication in patients.

One of the earliest attempts to treat TBE in animal models were performed with interferon inducers, nucleoside analogues and the two antibiotics tunicamycin and lincomycin. The latter drug was even studied in a clinical trial 20 years ago, showing positive results, but it was not licensed.

Strategic approaches to search for compounds with anti-TBE virus activity included i) repurposing of known broad-spectrum antivirals, ii) phenotypic screening, and iii) target-oriented enzymatic assays.

Various nucleoside analogues have been tested and broad-spectrum antivirals like ribavirin and galidesivir and FDA-approved antiviral drugs like Efivirenz and Favipiravir, the latter of which had been approved as an anti-influenza drug.

Perylene derivatives have been identified as potent inhibitors for TBE virus reproduction, and drugs that interact with the glycoprotein E or the RNA-dependent RNA polymerase and other non-structural viral proteins, like the NS2B/NS3 protease, were tested.

Not only have chemical drugs been screened but also natural compounds like plant extracts containing rosmarinic acid and flavonoids.

TBE has been neglected by medical chemists after the approval of vaccines, but in the past couple of years, new efforts, mostly by Czech and Russian teams, have led to new strategies and developments to study lead compounds suitable for clinical trials.

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