Spectrum of antiviral activity of 4-aminopyrimidine <i>N</i>-oxides against a broad panel of tick-borne encephalitis virus strains
Evgenia V. Dueva, Ksenia K. Tuchynskaya, Liubov I. Kozlovskaya, Dmitry I. Osolodkin, Kseniya N. Sedenkova, Elena B. Averina, Vladimir A. Palyulin, Galina G. Karganova
Abstract
Tick-borne encephalitis is an important human arbovirus neuroinfection spread across the Northern Eurasia. Inhibitors of tick-borne encephalitis virus (TBEV) strain Absettarov, presumably targeting E protein n-octyl-β-d-glucoside (β-OG) pocket, were reported earlier. In this work, these inhibitors were tested in vitro against seven strains representing three main TBEV subtypes. The most potent compound, 2-[(2-methyl-1-oxido-5,6,7,8-tetrahydroquinazolin-4-yl)amino]-phenol, showed EC 50 values lower than 22 µM against all the tested strains. Nevertheless, EC 50 values for virus samples of certain strains demonstrated a substantial variation, which appeared to be consistent with the presence of E protein not only in infectious virions, but also in non-infectious and immature virus particles, protein aggregates, and membrane complexes.